Current Challenges in the Treatment of Retinitis Pigmentosa
CubaHeal Research Department
Retinitis pigmentosa (RP) represents a rare and severely debilitating group of disorders affecting vision that have a genetic background and are slowly progressive by nature (1). Despite the continuing efforts of the scientific community directed towards the understanding and treatment of the disease, RP still remains incurable. Management of RP was investigated in various preclinical models, as well as in numerous clinical trials on humans in the United States, however, the effective and safe solution to this problem was not yet found.
Retinitis pigmentosa causes a progressive and irreversible vision damage caused by deterioration of photosensitive cells (especially rods) in the retina (2). Early symptoms usually represent the loss of the peripheral visual field, followed by further vision narrowing, which may eventually result in complete blindness. Treatment options in the United States are currently quite limited. The management of RP mostly includes vitamin supplementation, aiming to hold off the progression of the degenerative process. However, even vitamin supplementation, besides its’ limited effectiveness, has its safety concerns. Vitamin A supplementation is not recommended in certain individuals since it may cause fertility issues and severe osteoporosis (3). Preventative measures, such as avoiding light exposure in the early phases of the disease did not prove to be highly effective.
When reviewing the current treatment options, it seems that RP still represents a challenging task. In order to improve the quality of life of patients suffering from this degenerative and progressive disorder, Cuban experts have developed a sophisticated and effective method for the management of RP.
Solution Offered by Cuban Experts
The main treatment objective is to limit the disease progression by improving the vascularization of the retina. The management of RP in Cuba practiced now, that is focused on eye vascularization, has been developed and improved for more than two decades. The milestone of therapy is to bring as much blood, oxygen, and nutrients as possible to the eye. This is being performed by encouraging the development of blood vessels. There have been some attempts in Russia to transplant the stem cells that would develop into the healthy retinal tissue, however, scientists were mostly frustrated by failure since the stem cells could not successfully engraft due to the lack of the healthy vascular supply (4). Cells remodeling was also attempted; however, this study was suspended due to the lack of efficacy. Cuba offers a sustainable treatment option that focuses on limiting or completely inhibiting the progression of degenerative vascular changes in the retina. There are several treatment approaches that are being applied to the overall management plan. They include eye surgery, ozone therapy, electrostimulation and drugs (5).
A very sophisticated and unique surgical technique is used to increase the blood flow within the part of the eye responsible for providing blood supply to the retina. When this technique is performed, retina remains adequately nourished and oxygenated. This allows normal retinal function and prevents further deterioration of vision. By stimulating the blood flow within the retina, visual acuity increases, and retina is encouraged to grow, and not deteriorate. The final result is stabilization of the disease and rapid improvement in both central and peripheral vision (6). Ophthalmologists from all over the world refer their patients to Cuba, for this surgery to be performed due to its’ efficacy and safety.
It has been recognized that ozone improves cell metabolism, boosts the cell energy levels and exhibits antioxidant properties (7). The ozone is either administered rectally or being injected into the bloodstream. Ozone provides detoxification effects by blocking the harmful lipid peroxidation that occurs in retinal cells affected with retinitis pigmentosa. The ozonotherapy also promotes the blood flow surrounding retina, thereby directly improving the retinal function. In order to ensure the best possible results, the patient should receive 14 cycles of treatment during the course of the whole therapy.
Electrical stimulation produces a micro-massage effect that stimulates micro-circulation and lymphatic drainage. These effects promote electro-ionic balance and provide an additive effect to the ozonotherapy (8). This method has demonstrated a high efficacy. Another benefit of this treatment modality includes reinforcing the process of the perception of visual stimuli within the brain. The electro-stimulation includes the application of pleasant therapeutic electrical currents on the head, neck, soles of the feet, and palms of the hands. For the complete and best possible effect, 10-15 treatment sessions are needed to be performed. During the full treatment course, drugs including immune-modulators, oxide-reductive substances, minerals, and vitamins are administered to boost the treatment effects.
Cuban scientists investigated the effects of ozone treatment on the visual field in participants that had retinitis pigmentosa. This was a controlled, randomized and double-blind study, with the study design that ensures a high level of evidence. 68 participants were enrolled in the trial. Half of the subjects received ozone treatment, while the other half received placebo. The study demonstrated that three times more subjects in the ozone group experienced a significant improvement in the visual field, compared to those who received placebo. Subjects with early stages of the disease experienced greater improvement with more long-lasting effects, which underlines the importance of early intervention. Subjects at early phases of the disease also experienced more stable and sustainable treatment effects. In conclusion, this study showed that ozone treatment had beneficial effects on patients with RP.
Another double-blind, placebo-controlled study also evaluated the effects of ozone treatment in patients with retinitis pigmentosa. This study had an even greater number of participants (168). This study also demonstrated the significant improvement in patients treated with ozone therapy compared to patients that received placebo. Interestingly, approximately a half of the patients that had treatment response also succeeded to maintain the response for the longer period of time (9).
A study that investigated the redox-balance in patients with RP receiving ozone treatment concluded that ozone therapy represents a safe therapeutic modality since no side effects related to treatment were observed during the course of the trial. Therefore, ozone therapy can be safely administered to patients with RP without any risk of side effects (10).
Treatment of RP still represents a challenging task in the western countries. Vitamin supplements and avoiding excessive light are just not sufficient enough to provide any benefit to patients suffering from this severely debilitating illness. Various treatment approaches including stem cells transplantation and remodeling of the retinal cells have failed to demonstrate effectiveness. Stem cells failed to engraft, and retinal cell remodeling was not possible both because of the vascularization impairment that occurs in this serious illness. Cuban researchers and medical experts decided to target exactly this disease characteristic by improving the blood flow in the eye, which allows retina to properly function. Improvement of eye circulation ensures the adequate oxygenation of retinal tissue and postpones or completely stops the degenerative processes within the retina. Clinical trials and plenty of satisfied patients worldwide guarantee treatment success. Thousands of international patients referred to Cuba for the treatment of RP have experienced benefits following treatment. Clinics in Cuba still represent the only hope for people suffering from this genetic disorder. Cuban experts have found a solution to postpone or completely stop the development of the negative effects on the quality of life of patients suffering from RP.
Baumgartner, W. (2000). Etiology, pathogenesis, and experimental treatment of retinitis pigmentosa. Medical Hypotheses, 54(5), 814-824. Medline Plus Encyclopedia. Retrieved on July 1st, 2018, from http://www.nlm.nih.gov/medlineplus/ency/article/001029.htm Jayashree N Sahni et al. (2011). Therapeutic Challenges to Retinitis Pigmentosa: From Neuroprotection to Gene Therapy. Curr Genomics. 12(4): 276–284. Health Services International (Servimed) Inc. Retrieved on July 1st 2018, from http://www.healthservicecuba.com/retinitis-pigmentosa/ Centro Internacional de Retinosis Pigmentaria Camilio Cienfuegos de Cuba. Tratamiento cubano para la Retinosis Pigmentaria. Retrieved on July 1st, 2018, from http://www.infomed.sld.cu/instituciones/retinosis/quienesomos/quienesomos.html Garcia Layana, A. (2003). La cirugía de la retinosis pigmentaria en Cuba. Communication presented at Archivos de la Sociedad Española de Oftalmología, Madrid. Copello, M., Eguía, F., Menéndez, S., & Menéndez, N. (2003). Ozone Therapy in Patients with Retinitis Pigmentosa. Ozone: Science & Engineering, 25(3), 223-232. Berson, E., Remulla, J., Rosner, B., Sandberg, M., & Weigel-DiFranco, C. (1996). Evaluation of patients with retinitis pigmentosa receiving electric stimulation, ozonated blood, and ocular surgery in Cuba. Arch Ophthalmol, 114(5), 560-563. Pérez, L. J. (2004). Ozone therapy in retinitis pigmentosa. Communication presented at 4th International Symposia on Ozone Applications, Cuba. Menéndez, S., Hernández, F., & Copello, M. (2004). Ozone therapy and redox balance in patients with Retinitis Pigmentosa. Communication presented at 4th International Symposia on Ozone Applications.
During the decades of very rigorous sanctions brought by the United States, Cuba has managed to develop one of the biggest machineries for drug research and development. Due to the embargo, Cuba was practically forced to invest a substantial amount of funds into the medical research, in order to address the issue of the overall health of the population. Today, Cuba possesses a strong and sophisticated system for the production of state-of-art medicinal products. A large biotech and pharmaceutical group called BioCubaFarma gathers over 30 enterprises that are focused on investigating, developing and producing high-quality medicinal products intended for supplying domestic and international markets. Cuba currently markets the products 49 countries worldwide. A very resilient approach of Cuban experts in the field of drug research and development provides impressive results and continues to surprise the international scientific community with innovations and ideas.
Vaccination represents one of the public health medical interventions that has shown tremendous benefits in prevention, eradication and significant reduction of incidence of severe and debilitating infectious diseases worldwide. Due to the significance of vaccination for the public health, several leading organizations in the field of vaccination including the World Health Organization (WHO), Global Alliance for Vaccines and Immunization (GAVI) and the United Nations Children’s Fund (UNICEF) developed strategies to increase the immunization rate worldwide and disseminate the new technologies in the field of vaccination globally. All three organizations advocated for the research and development of polyvalent vaccines covering multiple diseases in order to make the process of vaccination more simplified and to cover more pathogens with only a single vaccine administration. In order to respond to the recommendations given by the leading organizations in the field of immunization, Cuba started with the challenging research and development program of vaccines.
Trivac HB is a polyvalent (combined) vaccine containing diphtheria anatoxin, tetanus anatoxin, B. pertussis whole cells and hepatitis B surface antigen. It provides protection against all the above-mentioned pathogens and represents the second ever produced tetravalent vaccine worldwide. Several years of sophisticated research regarding vaccine formulation, potency, safety and tolerability resulted in the successful registration of this medicinal product in 2004. Since then, Trivac HB has been successfully administered in children for the purposes of prevention of the aforementioned infections. This vaccine represents a state-of-art medicinal product due to several reasons. The tetravalent formulation allows the protection against the multiple pathogens, decreasing the need for multiple vaccinations resulting in the better acceptance of the immunization program both by the families and the sanitary personnel.
A careful process of selection of each component’s formulation resulted in inadequate protection in 97% of tested children, which is an impressive result. Safety of the vaccine was vigilantly monitored during the clinical trial process in each child. Less than half of the children experienced an adverse effect following administration of the vaccine. All reactions were mild in nature, with reversible fever being one of the most frequently reported systemic side effects. The vaccine was very well tolerated in children and the overall safety profile of the vaccine was assessed as non-toxic. Administration of the vaccine resulted in the production of high concentrations of antibodies against each pathogen conferring the high protection to the immunized children.
Haemophilus influenzae type b represented one of the main causes of severe bacterial meningitis in plenty of the countries worldwide until the introduction of a vaccine against this pathogen. The vaccine production includes the expensive process of extracting the capsular antigen prior to conjugation. Cuba has made an effort to develop a less costly method of vaccine production that would keep the vaccine potency. Cuban experts proposed the model of production of a synthetic bacterial antigen that would exhibit the same efficacy and would have an acceptable safety profile.
The safety, tolerability and preliminary efficacy of Quimi-Hib were investigated in two major Phase I clinical trials that were double-blinded and randomized in order to produce the highest level of evidence for obtained results. Populations investigated were adults and children (4-5 years old). Studies were conducted on healthy volunteers. The primary endpoints were safety and tolerability of the vaccine. The occurrence of local and systemic adverse events was monitored following the administration of the vaccine during 72h post-administration. The safety profile of the vaccine included the anticipated risks that were mild to moderate in nature and completely reversible. Vaccine efficacy was monitored using the contemporary methods of immunology for the screening of vaccine immunogenicity. The results obtained demonstrated high immunogenicity of the vaccine, meaning that the efficacy of the Quimi-Hib was comparable and equivalent to the traditional vaccine. With this vaccine, Cuba has successfully resolved the issue of high complexity and costs that was the main issue of the traditional vaccine. Quimi-Hib represents the innovative approach to vaccine development. Excellent results resulted in the registration of the vaccine in Cuba. This particular vaccine is now the part of the countries’ National Immunization Program.
The incidence of tick-born diseases is increasing worldwide in both humans and domestic animals. It has been estimated that approximately half of all ticks are Boophilus species. Therefore, an effective prevention of tick-borne diseases should target the control of infestation by this specific species. Cuba has developed an efficient method for the protection against tock-borne diseases, which directly resulted in significant reduction of tick-related infestations. This vaccine offers the cost-effective method for the prevention of tick-born diseases that is benevolent for the environment. The development of the so called Bm86 gut antigen, which is the active ingredient of the Gavac vaccine, has brought the feasible solution to control the tick infestations. The investment of knowledge, expertise, and funds to develop such a sophisticated method of prevention in Cuba will also contribute to further research and development of other molecular technologies towards the discovery of new methods for inhibition of tick infestation.
Heberbiovac HB represents a vaccine developed for the prevention of hepatitis B infection. This vaccine demonstrates also a therapeutic potential and can be used as an adjunctive treatment for patients suffering from hepatitis B infection. This vaccine was developed in Cuba according to the recommendations tailored by the World Health Organization. The vaccine contains hepatitis B surface antigen, an active ingredient responsible for effective prevention of the hepatitis B infection. This vaccine has also shown efficacy in the treatment of both acute and chronic forms of the disease, as well as in the management of hepatocellular carcinoma. Interestingly, when receiving the vaccine, 95% of newborns of infected mothers are protected during life.
Heberviron was developed in Cuba for the treatment of hepatitis C infection. Not only that it has a significant cure rate, but it also exhibits a very good protection against the recurrence of the infection. The treatment duration when using Heberviron lasts for 7 days. This is quite important since the shortened treatment duration reduce the risk of serious side effects that may occur with the use of this drug. The combination of interferon and antiviral drug ribavirin as the active ingredients of Heberviron allow the better treatment outcomes and increase the success rate of treatment against the hepatitis C infection. Heberviron represents the state-of-art product of Cuban drug research and development.
Heberon Alfa R
Cuba has an advanced biotechnology industry. The development of interferon alfa-2b designed for intramuscular, intralesional, intravenous or subcutaneous injection confirms this statement. Heberon Alfa R structure is adapted so that the drug can be used in different modes of administration as stated above. Heberon Alfa R contains anti-tumor and anti-virus properties. It is intended for use in patients suffering from serious diseases such as chronic hepatitis B and C, HIV-induced Kaposi’s Sarcoma, malignant melanoma and many other neoplastic disorders. This drug is also approved for the use in children, where administration of Heberon Alfa R was proven safe and effective in children and adolescents.
Heberkinasa was created using the recombinant technology in order toprovoke a rapid and more effective thrombus degradation. Heberkinasacauses thrombus dissolution and recanalization of the affected vessel. The drug also prevents the tissue affected by ischemia to undergo necrosis. It has been demonstrated in clinical trials that recombinant streptokinase restores the ventricular function of the heart following myocardial infarction. The drug decreases the risk of pulmonary embolism and facilitates the elimination of embolus. The formulation of this drug does not contain immunogenic albumins, which directly reduces the risk of hypersensitivity and immune-mediated reactions, improving the drug’s safety profile.
Cuba produces the so-called highly active antiretroviral therapy (HAART). This treatment is intended for those infected with the HIV virus and other less common retroviruses. The formulation of the drug is specifically designed to reduce the side effects of conventional HAART drugs. This formulation reduces the abnormalities in blood cells and reduces the trend of hemoglobin depletion during treatment, which improves the overall tolerability profile of the drugs. Cuban antiretrovirals also have need shown to increase the number of virus-free CD4 lymphocytes. Decreased mortality and mortality from HIV infection has been also demonstrated in clinical trials.
Hebertrans is a highly sophisticated product containing the extract of leucocytes derived from human leucocytes that are used as the modulator of the defective immune response. The main characteristic of this medicinal product is that Hebertrans produces no side effects. It may be used in patients with defect immune system such as those receiving cytotoxic cancer treatment, those with immune deficiency (both acquired or congenital) or patients with autoimmune and allergic conditions. Hebertrans leads to the effective stabilization and normalization of the immune response.
Heberitro is a recombinant human erythropoietin. It stimulates the natural production and maturation of red blood cells, increasing the mass of red blood cells within the bloodstream. It is effective in various types of anemia caused by iron depletion. Its’ effectivity has been especially demonstrated in patients suffering from chronic kidney failure, those on HAART anti-HIV therapy, as well as in patients undergoing radiotherapy.
The sophisticated technology in Cuba allowed the development of so-called granulocyte colony stimulating factor (GCSF). Hebervital directly increases the production and maturation of granulocytes, especially neutrophils. Neutropenia is a serious risk in a patient receiving chemotherapy and may lead to the development of severe infections, even sepsis. GCSF successfully increases the number of granulocytes necessary for the effective immune response against infections. Hebervital directly decreases the risk profile of chemotherapy by mitigating the risk of severe neutropenia or bone marrow failure.
LeucoCIM is a granulocyte colony-stimulating factor (G-CSF) used for the treatment of neutropenic patients. Drug use has been proven beneficial in patients having myelosuppression following cytotoxic treatment, patients with myeloid leukemia and those with neutropenia caused by HIV/AIDS. The drug also prevents the development of bone marrow suppression in patients undergoing bone marrow transplantation.
Gilda Torano et al. Phase I Clinical Evaluation of a Synthetic Oligosaccharide-Protein Conjugate Vaccine against Haemophilus influenzae Type b in Human Adult Volunteers. Clinical Vaccine and Immunology. September 2006 vol. 13 no. 9 1052-1056.
Dania Bacardí et al. Preclinical safety testing of the Quimi-Hib® vaccine adjuvanted with aluminum phosphate during product development. Biotecnología Aplicada 2013;30:118-124.
Néstor S. Expósito, Daniel Cardoso, Eduardo Martínez, Yanelis Herrera, Karelia Cosme, Pablo A. Díaz4, Yayrí C. Prieto, Zoe Núñez, Mabel Izquierdo, Orestes Mayo, Joel Pérez, Luis C Hidalgo. TrivacHB: A Cuban Polyvalent Vaccine. Biotecnología Aplicada 2006; Vol.23, No.2.
Jose de la Fuente et al. A ten-year review of commercial vaccine performance for control of tick infestations on cattle. Animal Health Research 2007. 8(1):23-8.
Castañeda Guillot C, et al. Long term study of the treatment with recombinant alfa 2b interferon in chronic active hepatitis due to B virus in children and adolescents. G E N. 1994 Oct-Dec;48(4):219-25.
CECMED. Resumen De Las Características Del Producto. Estreptoquinasa recombinante. Last revision: 27 Dec 2013.
It has been estimated according to the data published by the World Health Organization that 1 in 160 children worldwide suffers from autism. The exact number is quite challenging to estimate for various reasons. It is presumed that Cuba has a lower rate of children with autism spectrum disorder when compared with the United States. Yet, Cuba has taken autism quite seriously and constantly develops and improves strategies aimed to increase the quality of life of children with this serious medical disorder and their families. The country has established specialized centers focused both on the treatment of children and inclusion of the families in the society, which is of course absolutely costs free. In 2013, Cuba was the country to host the First International Forum on Autism and Inclusion. This conference gathered the globally recognized experts in the field of autism spectrum disorder (ASD). The focus of the conference was to establish methods and discuss the significance of an early diagnosis of ASD and effective inclusion of such families in the society. The conference alone mirrors the country’s efforts to seek for the best possible ways to make the lives better for children with ASD and their families.
Treatment of Autism in Cuba
The program aimed to increase the quality of life of persons living with ASD is coordinated by the Cuban Ministry of Public Health and Ministry of Education. Other public sectors including culture, media, and sports institutions are also involved in the program for helping ASD individuals to reach the best of their abilities. The program consists of individualized, multi-disciplinary training aimed at developing and empowering skills. The ASD individuals also receive specialized education and advocacy support. The individualized treatment is tailored by the specialized Diagnostic Commission when the type and severity of the disease are taken into consideration. Treatment is focused on early intervention.
The treatment for ASD is conducted in the peaceful and comfortable environment in order to ensure the best possible effects of the treatment plan and to allow the improvement the patient’s mental and physical abilities. The objective of each individualized treatment plan is to ameliorate the symptoms of the disease and improve the child’s learning capacity. As already mentioned, the treatment is tailored according to the individual needs of each child.
Each medical facility that deals will the treatment of autism is equipped with rooms that resemble those in a hotel (cable TV, phone, dry cleaning services). The facility contains sauna, pool, gym, internet access, shops, and pharmacies.
Treatment Stage 1: Assessment
The first stage of treatment consists of detailed assessments and evaluations that include laboratory and imaging analyses, and consultations with different specialists. The child is examined and evaluated by a pediatrician, neurologist, psychologist, speech therapist, and psychiatrist. The laboratory panel consists of hemogram, serology testing, serum glucose, sedimentation, urine analyses, creatinine and liver functions tests. Additionally, specific testing consists of magnetic resonance brain imaging, evoked potentials, and electroencephalography. Each patient undergoes logopedic assessment, neuropsychological evaluation, Brunet-Lezine scale evaluation as well as psychotherapeutic treatment assessment. Within the first stage, parents are also introduced to the team of experts and the treatment plan is referred to the parents once completed. The phase duration is approximately one week, depending on the patient’s characteristics.
Treatment Stage 2: Therapy and Rehabilitation
The duration of actual treatment is approximately 30 days, but this may vary depending on the patient’s characteristics. The tools that are used in the treatment of autism include equine therapy, occupational treatment, language therapy, sensorial stimulation, ozone treatment and trans-cranial electric stimulation if needed (in hyperkinetic patients). Language treatment is carried out each day. In the beginning, the language rehabilitation sessions last one hour during the day, but this is extended later to two sessions each day.
Language rehabilitation usually lasts 20 days. During this treatment, the child is being constables evaluated by the experts and the progress is being monitored. Based on the effects of treatment, the language rehabilitation process is further re-tailored based on the response of each child. Therefore, each treatment protocol is being adjusted by the characteristics of each child. Language rehabilitation is broad and intensive. During each treatment, specialist conducts sensorial stimulation techniques such as facial massage. Specialized teams also work with family members or companions in order to ensure the best possible communication results. Family members or companions are taught to conduct language exercises and sensorial stimulation as continuing the language training after the child leaves the facility is essential for obtaining good treatment results.
Occupational treatment is also a very important feature of the overall rehabilitation program. This treatment aims to help the patients overcome the obstacles of physical and mental barriers present within the ASD, which restrict the everyday activities such as self-care, productivity, and participation in leisure activities. The treatment is conducted each day in two sessions. Specialists work with object identification, images projection and touching through interactive and didactic games.
As a part of occupational treatment, the children are engaged in outdoor activities. Engaging and stimulative games and exercises are being tailored for each child in order to learn about the surroundings. This treatment is also tailored based on the child’s preferences. Children are stimulated with colors, various physical activities including swimming in the pool, soccer, horseback riding etc. The specialists carefully monitor the children and adjust the program based on the child’s response to each stimulation. The length and duration of occupational therapy are also assessed based on the child’s characteristics and the progress being made with this treatment approach. This treatment has a goal to improve the patient’s productivity, physical performance, and sensorial activity.
Final Report and Recommendations
Once the treatment is considered completed, the experts will tailor the final report consisted of the diagnosis, severity, and prognosis of the ASD. Based on the vigilant monitoring of the child during each stage of treatment, the experts will issue the comprehensive recommendations for each child regarding further treatments and ASD management approaches.
Cuba is investing a lot of effort in advancing the management of children suffering from ASD. Prestigious medical centers in Cuba have programs based on the extensive international experience in autism management. Treatment protocols for ASD are in line with the globally accepted international medical standards. Cuba invests in the training of staff that deals with kids suffering from ASD. There is still a lot to be learned about ASD in order to provide the best possible treatments for ASD patient and their families. Cuba has proven to take this issue seriously and professionally.
Life expectancy of Cuban population has increased significantly over the past decade. In 2014, an average life expectancy was shown to be 78.5 years (1). It is predicted that approximately a third of the entire population in Cuba is going to reach the age of 60 by the year 2030 (2). The increased life expectancy, increase in the prevalence of elderly population combined with an unhealthy lifestyle represents a significant risk of increased cancer burden for the people living in Cuba. In 2012, cancer became a leading cause of death in Cuba, counting for approximately a quarter of all fatal outcomes (3). Due to these data, Cuba has developed strong mechanisms of cancer prevention, management, and research that are comparable to those in the developed countries. A comprehensive and systematic approach to cancer prevention, early diagnosis, treatment and palliative care has shown results including increased survival and better quality of life in patients suffering from cancer (4).
The strategy of fighting cancer in Cuba has been established a decade ago. The main objectives include education and communication of cancer risk factors to the general population, early detection of cancer in the primary healthcare setting, treatment and supportive care in highly specialized institutions, as well as research and development of innovative therapeutic modalities against various types of cancer (5). A very developed network of primary healthcare institutions enables the physicians to discover cancer in the early stages. These patients are then referred to specialized institutions where an adequate diagnostics and staging are being made, followed by cancer management techniques. Following the implementation of the abovementioned strategy, cancer survival rates in Cuba have shown increasing trends, which are comparable to those in developed countries.
Due to an increased prevalence of cancer, Cuba has invested a significant amount of funds to cancer treatment and research in order to achieve the highest standards in cancer management. Some of the fascinating achievements of Cuban approach to cancer will be reviewed in this article.
NATIONAL INSTITUTE OF ONCOLOGY AND RADIOBIOLOGY (INOR)
INOR serves as an international medical center that provides advanced and highly sophisticated medical care for cancer patients from all over the globe. Highest standards in the management of cancer are implemented at this institution with the goal to cure, improve and increase the quality of life of each patient that seeks medical attention. Advanced treatment modalities, holistic approach to each patient, integrative rehabilitation techniques combined with the use of natural healing methods are just some of the services aimed to increase patient welfare at this institution. INOR conducts scientific and educational activities related to the nature and biology of cancer. Various clinical trials are being conducted at this facility in order to investigate and evaluate novel and promising cancer treatment regimens (6). Patients from more than 50 counties worldwide including Europe, USA and Canada have been treated at this institution with exceptional quality of care.
SUCCESSFUL MANAGEMENT OF LEUKEMIA
In Cuba, the overall survival of kids suffering from acute lymphoblastic leukemia following standard therapeutic protocols is approximately 85% in standard risk patients (7). The improvement after the application of last generation cytotoxic treatments is seen in approximately 98% of children. Bone marrow transplants are performed with high success rates. Additionally, Cuba performed transplantation of cord blood hematopoietic stem cells in order to treat various forms of leukemia. All of the treatments are totally free of charge for all Cubans.
NON-MELANOMA SKIN CANCER
Skin cancer is among the most frequent cancers in Cuba (8). The challenges in the treatment of nonmelanoma skin cancers include non-resectable, aggressive and recidivant forms, which are difficult to treat and often lack in proper and effective therapeutic modalities. The successful management of nonmelanoma skin cancer in Cuba is reflected in the application of the novel combination of two interferons. More than 400 patients have been treated with this combination with high rates of success, reaching clinical remission in approximately 65% of cases (8).
Oral cancer was among the most frequent forms of cancers in Cuba. The development of preventative actions including regular oral examination of individuals at least once a year led to significant decrease in the incidence of advanced oral cancer. The vigilant approach to early detection of oral cancer resulted in significantly higher detection rates of low-grade oral cancers that are more sensitive to treatment and have much better prognosis (9).
Early detection of cancer remains the focus in the fight against malignancy in Cuba. Highly developed primary health care system represents a pillar stone of Cuban medical care. The early detection of malignancy on a primary health care level directly resulted in significantly better therapeutic outcomes in patients suffering from various types of cancer. The increasing aging of Cuban population increased the risks of developing malignancies. Therefore, Cuba has developed tertiary centersfor cancer diagnostics, staging, treatment and research. These centers are operating with the highest international standards in cancer management and offer innovative approaches in cancer treatment that are completely free of charge for any Cuban, rating the success of cancer management in Cuba to be among those in highly developed countries.
1. Oficina Nacional de Estadistica. Anuario demográfico 2014. http://www.one.cu/anuariodemografico2014.htm. [Online] 2. National Statistics Bureau (CU). El envejecimiento de la población cubana. http://www.one.cu/publicaciones/cepde/envejecimiento/ envejecimiento2008.pdf. [Online] 3. Dirección Nacional de Registros Médicos y Estadísticas de Salud. Anuario Estadístico de Salud de Cuba. http://files.sld.cu/dne/files/2015/04/anuario-estadistico-de-salud-2014. [Online] 2018. 4. WHO. Cuba – Battling cancer with biotechnology. http://www.who.int/features/2013/cuba_biotechnology/en/. [Online] 2018. 5. Teresa Romero Pérez, Yaima Galán Alvarez and Rolando Camacho Rodríguez. THE BURDEN OF CANCER IN CUBA AND CURRENT STRATEGIES FOR CANCER CONTROL. http://www.cancercontrol.info/cc2016/the-burden-of-cancer-in-cuba-and-current-strategies-for-cancer-control/. [Online] 2018. 6. INOR. National Institute of Oncology and Radiobiology. http://instituciones.sld.cu/inor/. [Online] 2018. 7. Results of the treatment of child Acute Lymphoid Leukemia in Cuba. Alejandro, González-Otero et al. s.l. : Revista Cubana de Hematologia, Inmunologia y Hemoterapia, 2014, Vol. 30(1). 36-46. 8. HeberFERON, formulation based on IFNs alpha2b and gamma for the treatment of non-melanoma skin cancer. Lorenzo, Anasagasti-Angulo et al. 10(6), s.l. : Australasian Medical Journal, 2017. 9. Research on cancer prevention, detection and management in low- and medium-income countries. R. Sankaranarayanan, P. Boffetta. 10, s.l. : Annals of Oncology, 2010, Vol. 21. 1935–1943.
Canadian Woman’s Successful Use of Cuban Vaccine Gives Mesothelioma Patients Hope
A Cuban vaccine called CIMAvax EGF, which is currently undergoing U.S. testing for its effectiveness in treating mesothelioma and other cancers, has apparently saved the life of a Canadian woman diagnosed with non-small cell lung cancer. Judy Bryden of Regina, Saskatchewan was originally diagnosed with the terminal form of cancer back in 2016 and given just a year to live.
She initially pursued traditional forms of treatment in Canada, including chemotherapy and radiation therapy. After that protocol failed to stop the advancement of her disease she and her husband began researching alternative treatments, and that is when they learned about the success that the Cubans were having with their remarkable cancer vaccine. They contacted an outfit called CubaHeal, which is specifically set up to help people from outside of Cuba to visit the country for treatment, paid a small fee for the process, then traveled there for treatment and to purchase several doses of the vaccine to bring back to her home. The total cost of the trip was $14,500, a fee that was well worth it as her physician says she is now in remission.
CIMAvax has long been discussed as offering great hope for mesothelioma patients. It activates the immune system against a specific protein that has been identified as facilitating cancer cell growth. It is already in clinical trials in the United States following an agreement between the Roswell Park Comprehensive Cancer Center in New York and the Cuban government that was struck in April of 2015. The Phase I clinical trial began in January of 2017 and is expected to take at least two years, followed by another year or two for the Phase II portion of the trial. The drug has already been approved for use in Bosnia and Herzegovina, Colombia, Cuba, Paraguay and Peru.
A Regina woman wants to spread the word about a vaccine she received in Cuba that she says has kept her alive.
Judy Bryden was diagnosed with lung cancer in 2016, after returning home from a trip with a cold. She underwent numerous scans and, in November 2016, she began chemotherapy. Bryden said the chemotherapy nearly killed her and didn’t cure the cancer. She went through five radiation treatments, and the cancer survived. Following that, a doctor recommended palliative chemotherapy, suggesting Bryden only had one year to live.
“When they told me I had a year to live, I said I was going to prove them wrong. I didn’t know how, but I was going to prove them wrong,” Bryden said.
Bryden refused a second round of chemo. It was at that time that her husband Lorne Bryden first heard about the Cimevax EGF vaccine.
“I searched the internet and found a company called CubaHeal in Brantford, Ontario,” Lorne said. “They were able to put the whole thing together for us, for a fee, of course.”
“When they found (CubaHeal), there was something about it that just felt right. It just felt right at its core,” said Pamela Bryden, Bryden’s daughter.
Lorne submitted Bryden’s medical information, and went on to pay $135. Bryden was approved for treatment, but they had to travel to Cuba.
The vaccine is currently not available in Canada. Health Canada says that is not because of any known safety concerns about the drug. Instead, Health Canada simply does not actively solicit new drug submissions. No application has been submitted for Cimevax EGF yet.
The vaccine works by targeting the epidural growth factor (EGF) which is a protein found naturally in the body. In certain types of cancers, the body produces too much EGF, forcing the cells to grow and divide uncontrollably.
“The company is responsible for submitting an application to Health Canada, so their product can be approved on the Canadian market. Only once we receive that application, will we review an application,” Health Canada spokesperson Renelle Briand said.
The Brydens returned from Cuba in March 2017, with four doses to be injected every 14 days. A CT scan of Bryden this past February found no cancer.
The treatment isn’t cheap. A trip to Havana, plus a year’s supply of injections, costs about $14,500. But it’s still much less than the $65,000 dollar treatment Lorne found for sale in Tijuana, Mexico.
“I wish Cimevax was here for people, because it’s $1,000 a month that we pay,” Bryden said. “It’s worth it.”
Bryden hopes her story encourages others to try the treatment themselves. A recent CT scan shows the cancer has not spread, and CubaHeal has approved another year of vaccines for Bryden. Lorne is planning to leave on March 19 to go pick up the vaccine.
The incidence of lung cancer has risen dramatically. It is already projected that near two million new lung cancer cases will occur in the United States resulting in approximately half a million fatal outcomes in 2018 (1). According to the data provided by the Centers for Disease Control and Prevention (CDC) lung cancer has been assessed as a second leading type of cancer in both men and women. Screening modalities of contemporary medicine have not yet addressed the issue of diagnosing lung cancer in early stages, resulting in capturing this condition as a progressive disease in most of the patients. Conventional treatment of non-small cell lung cancer (NSCLC) including surgery, chemotherapy, and radiotherapy has very limited efficacy in advanced stages of NSCLC and has been associated with serious toxicities. Additional problem represents cancer recurrence after conventional treatment occurring in approximately 40 percent of patients after a period of one year (2).
Cuba has produced 33 new drugs for treating cancer by the year 2012 (3). The fastgrowing medical scientific research in Cuba continues to produce innovative medicinal products, aiming to significantly increase the quality of life in patients suffering from most complex and serious medical conditions.
An interesting and novel therapeutic approach that includes programming of body’s own immune system to fight cancer cells was investigated in Cuba. The research prompted the development of immune therapies including therapeutic vaccines. Vaxira is a therapeutic vaccine developed to treat NSCLC. The medicinal product was registered in Latin American countries in 2013, after promising results shown in phase II/III study involving patients with advanced and progressive NSCLC (4). In this study, patients that received Vaxira showed a significant increase in overall survival comparing to patients who received placebo. Another study that involved 180 patients investigated the effects of Vaxira following conventional treatment for late-stage, recurrent NSCLC. The results clearly showed decrease in the progression of NSCLC which directly resulted in prolonged survival periods in patients who previously received the first-line treatment for NSCLC (5). Finally, a randomized, open-label clinical trial that involved 1082 patients with advanced NSCLC, who received standard first-line therapy, showed the response of stable disease after administering Vaxira (6).
The safety profile of Vaxira was also evaluated in clinical trials described above. In a phase I study of Vaxira for NSCLC that was focused on patient safety, no serious adverse events that were considered to be related to treatment have occurred. Related events included local reactions at the administration site including pain, redness, and induration. Reactions were mild and reversible in nature (7). Toxicity in more advanced clinical trials of Vaxira was similar to those in the phase I study described above. Cases of a headache, joint pain, and fever were also observed, however, all events were mild to moderate in nature.
Vaxira was initially developed in Cuba. The well-recognized efficacy of this medicinal product in the treatment of NSCLC prompted multiple investigations for a wide variety of conditions including melanoma, breast, and lung cancer at different locations worldwide (Spain, Brasil, Singapore).
It has been recognized that malignant cells express epidermal growth factor (EGF) receptor in higher amounts than non-malignant cells. This particular characteristic of tumor cells enables them to grow more rapidly and spread more aggressively (8). CIMAvax-EGF vaccine expresses anti-cancer activity by stimulating the production of anti-EGF antibodies, which inactivate the circulating EGF directly inhibiting the proliferative nature of malignant tumor (9).
The effectiveness of CIMAvax-EGF was demonstrated in Phase II clinical trial, conducted in 80 patients with NSCLC, who were previously treated with standard platinum-based chemotherapy. Patients treated with CIMAvax-EGF showed increased survival trends (10). A Phase III open-label efficacy study that was conducted on the sample of 405 patients that suffered from a late-stage NSCLC showed a significant increase of 5-year survival in those who received the vaccine. The 5-year survival rate for vaccinated patients was approximately 16% in comparison to control group, where 5-year survival was 6% (11). Interestingly, it has been noted that following vaccination, levels of EGF remained low in patients with long-term survival (more than 2 years). EGF level proved to be a powerful prognostic factor for overall survival and cancer recurrence (12). CIMAvax-EGF can be administered concomitantly with standard platinum-based cytotoxic treatment for NSCLC. It is advised to administer the vaccine during or prior to platinum-based treatment in order to achieve the best possible response and efficacy (13).
The safety profile of CIMAvax-EGF was evaluated in the aforementioned clinical trials. The most frequent reactions associated with the use of CIMAvax-EGF were local administration site reactions including pain and redness, as well as systemic reactions such as fever, headache, chills, and shortness of breath. It is clear that the benefits of this vaccine outweigh the risks related to the administration of CIMAvax-EGF.
Due to the extensive therapeutic potential of CIMAvax-EGF, a Phase IV clinical trial was launched that enrolled more than 1000 patients with NSCLC (14). It was shown that the use of this vaccine is safe and beneficial to patients with NSCLC. Preliminary evidence suggested that besides the increase in overall survival, CIMAvax-EGF improved the quality of life of enrolled patients by increasing the emotional well-being and reducing symptoms and signs of fatigue.
This revolutionary medicinal product prompted new research focused on other types of cancers including prostate cancer and gave hope both to the scientific community and patients that the cure for NSCLC is on the horizon.
1. Cancer statistics, 2018. Siegel RL, Miller KD, Jemal A. s.l. : CA Cancer J Clin, 2018, Vol. 68(1). 7.
2. Survival after recurrent nonsmall-cell lung cancer after complete pulmonary resection. Sugimura H, Nichols FC, Yang P, Allen MS, Cassivi SD, Deschamps C, Williams BA, Pairolero PC. s.l. : Ann Thorac Surg, 2007, Vol. 83(2). 409.
3. Profit vs health? Comparing the business models of Cuban and US pharma. Baden, Denise, Davies, Courtney and Wilkinson.s.l. : Monograph (Working Paper), Southampton, GB University of Southampton 12pp, 2015.
4. A randomized, multicenter, placebo-controlled clinical trial of racotumomab-alum vaccine as switch maintenance therapy in advanced non-small cell lung cancer patients. Alfonso, S et al. s.l. : Clin Cancer Res, 2014, Vol. 20(14). 3660-71.
5. Active immunotherapy in patients with progressive disease (PD) after first-line therapy. Gomez, R.E., Alfonso, S et al. s.l. : 49th Annu Meet Am Soc Clin Onco (ASCO), 2013. Abst 3086.
6. Trial proactive: A prospective, randomized, multicenter, open label phase III study of active specific immunotherapy with racotumomab plus best support treatment versus best support treatment in patients with advanced non-small cell lung cancer. Roberto E Gomez, Amparo Macias, TaniaCrombet, Ana Maria Vazquez et al. s.l.: Journal of Clinical Oncology.
7. An anti-idiotype vaccine elicits a specific response to N-glycolyl sialic acid residues of glycoconjugates in melanoma patients. Alfonso, M et al. s.l. : J Immunol, 2002, Vol. 165(5). 2523-9.
8. Molecular epidemiology of lung cancer and geographic variations with special reference to EGFR mutations. Mitsudomi, T. s.l. : Transl Lung Cancer Res, 2014, Vol. 3(4). 205-11.
9. Clinical development and perspectives of CIMAvax EGF, Cuban vaccine for non-small-cell lung cancer therapy.Rodríguez PC, Rodríguez G, González G, Lage A. s.l. : MEDICC Rev, 2010, Vol. 12(1). 17-23.
10. Phase II randomized controlled trial of an epidermal growth factor vaccine in advanced non-small-cell lung cancer. Neninger Vinageras E, de la Torre A, Osorio Rodríguez M, Catalá Ferrer M, Bravo I, Mendoza del Pino M, Abreu Abreu D, Acosta Brooks S, Rives R, del Castillo Carrillo C, González Dueñas M, Viada C, García Verdecia B, Crombet Ramos T, González Marinello G. s.l. : J Clin Oncol, 2008, Vol. 26(9). 1452-8.
11. A Phase III Clinical Trial of the Epidermal Growth Factor Vaccine CIMAvax-EGF as Switch Maintenance Therapy in Advanced Non-Small Cell Lung Cancer Patients. Rodriguez, PC et al. s.l. : Clin Cancer Res, 2016, Vol. 22(15). 3782-90.
12. Biomarkers related to immunosenescence: relationships with therapy and survival in lung cancer patients. Saavedra D, García B, Lorenzo-Luaces P, González A, Popa X, Fuentes KP, Mazorra Z, Crombet T, Neninger E, Lage A. s.l. : Cancer Immunol Immunother, 2016, Vol. 65(1). 37-45.
13. Combining an EGF-based cancer vaccine with chemotherapy in advanced nonsmall cell lung cancer. Neninger E, Verdecia BG, Crombet T, Viada C, Pereda S, Leonard I, Mazorra Z, Fleites G, González M, Wilkinson B, González G, Lage A. s.l. : J Immunother, 2009, Vol. 32(1). 92-9.
14. CIMAvax EGF (EGF-P64K) vaccine for the treatment of non-small-cell lung cancer. Crombet Ramos T, Rodríguez PC, Neninger Vinageras E, Garcia Verdecia B, Lage Davila A. s.l. : Expert Rev Vaccines, 2015, Vol.14(10). 1303-11.
Back in 1978, a conference was held in Almaty (formerly Alma-Ata), the city in Kazakhstan where the one of the most significant public health declarations emerged. One of the most significant excerpts of the Declaration was the profound role of primary health care in establishing the concept of „Health for All”According to the World Health Organization (WHO), an adequate availability (adequate supply of healthcare), accessibility (adequate distribution of healthcare) and acceptability (treating all patients with dignity) of a healthcare system is required to ensure the best possible health outcomes in a population. Cuban healthcare system is established to meet the aforementioned standards, and by many criteria, this system is currently unique and one of the most efficient healthcare systems worldwide (1) .
National Healthcare Policy Goals
Back in 1983, Cuba introduced a Public Health Law establishing basic principles of the healthcare organization. The main characteristic of this healthcare system is that healthcare represents a right that is available equally to all and is completely free of charge (2) . One of the major differences between Cuban and American healthcare principles is that in Cuba, healthcare is the responsibility of the state. Additionally, the Law promotes global cooperation of health systems and its professionals.
On the contrary, a profit-driven healthcare system in the United States results in great imbalances of knowledge and quality of health services, and more importantly, creates a population that cannot afford a proper healthcare leading to healthcare quality being unpredictable and dependent on the financial state of each individual (3) .
National Health System of Cuba, that has been founded on a very effective primary health care, is producing impressive results. Rates of immunization are amongst highest in the world. Over 98 percent of children are vaccinated against 13 illnesses by the age of 2 (4) . Antenatal care is provided to 95 percent of pregnant women and mortality rate of infants is 5 per 1000 births. Control of blood pressure at least once per year is available to the entire population (5) . As a result of exceptional healthcare outcomes, Cuba is officially at the top of the list of countries that meet the United Nation’s Millennium Development Goals, focusing on the social components of healthcare services.
The pillar stone of Cuban healthcare system is the primary healthcare institutions. A community-based polyclinic, covering a population of 30000 to 60000 individuals represents a centerpiece of primary health care. These polyclinics serve as a hub for family doctor and nurse practices, where each family doctor covers a population of approximately 600 to 800 individuals. The polyclinics are also centers for education and training of the new physicians, nurses and other healthcare sciences students. Interestingly, Cuba was one of the first countries worldwide which introduced the concept of family care physicians (6) . This model of healthcare organization increased the prevention of chronic conditions such as diabetes, hypertension, heart failure, obstructive pulmonary disorders, and significantly decreased the need for “high-tech“ technologies in diagnosing and treating diseases (7) .
The polyclinics are advancing even today. The goal is to extend the range of health services at the primary healthcare level. Polyclinics are being equipped with ultrasound, X-rays, endoscopy, emergency care, immunization, rehabilitation services and many other (1) . Approximately 800 to 1000 patients use the services daily.
Drug Research and Development
Cuba is investing a significant amount of funds into drug research and development. The approximately US $1 billion investment in pharmaceutical and biotech industry resulted in the production of innovative medicines, vaccines and diagnostic kits that are now being sold internationally (8) . The most significant achievements of drug development will be discussed here.
Serogroup B meningococcal vaccine
Cuba developed and registered this vaccine back in 1989 in order to prevent childhood meningitis. The United States Food and Drug Administration (FDA) registered this exceptional medicinal product only recently, in 2014, when it was manufactured by Pfizer.
The drug has been developed in the CIGB (Center for Genetic Engineering and Biotechnology) of Havana. It is a combination of two interferons. The result of its complex mechanism of action is tumor growth suppression, particularly basal cell carcinoma (CBC) no matter of its size, location and subtype. Although most of the skin carcinomas can efficiently be cured surgically, in some cases, it’s not that simple (face- surgical procedures are often mutilating causing severe reduction of the quality of patient’s life).
The drug was registered in Cuba in 2006 and, since then, 15 more countries registered it, and more than 100.000 patients around the world have received the treatment with incredible results. The target patients are those with chronic diabetic ulcers resistant to other modalities of treatment (high amputation risk). By its structure, Heberprot-P is an epidermal growth factor (EGF), and it’s administered by injection, locally.
According to the clinical research, Nimotuzumab, due its safety profile, is an excellent ad-on therapy for the patients diagnosed with squamous cell carcinoma of the head and neck (SCCHN). The study blished back in 2009, clearly demonstrated that Nimotuzumab, combined with radiotherapy, triples the 30-month survival rate compared to the group of patients who received radiotherapy only.
1994 was the year when Cuban Center for Molecular Immunology started investigating this medicinal product for the purpose of treating non-small cell lung cancer (NSCLC). Studies have shown a significant increase in survival of NSCLC patients. Earlier this year, more than twenty years after the product was developed in Cuba, Roswell Park Cancer Institute in Buffalo, New York, decided to initiate the clinical trial in order to investigate the efficacy and safety of this vaccine for the treatment of patients suffering from NSCLC.
Melagenina Plus (Vitiligo)
The drug is an alcoholic extract from human placenta. The Melagenina Plus lotion is applied once a day to the affected areas. It causes the repigmentation by stimulating melanocytes in a chromic region of the skin (white patches). Available all around the world for more than 20 years, it claimed the title of miraculous vitiligo drug.
This interesting vaccine received approval in Latin American countries back in 2013, following completion of phase II/III study involving patients with advanced and progressive NSCLC. Racotumomab showed a significant increase in survival of patients suffering from end-stage NSCLC. This promising medicinal product is being evaluated in a multinational phase III study aiming to investigate the effects of this vaccine on health outcomes in NSCLC patients (NCT01460472).
In conclusion, it appears from the above that the industry in the United States still does not possess adequate mechanisms in providing innovative medicinal products when compared with Cuba.
HIV/AIDS, Ebola Outbreak
Cuba was the first country in the world recognized by the WHO for eliminating mother-to-child transmission of HIV and syphilis (9) . According to the Center for Disease Control (DCD), up until 2014 in the United States, there were 5419 deaths among the population who acquired HIV through perinatal transmission. Recently, Cuba has sent a large group of physicians in order to fight the Ebola outbreak.
These were just some of the characteristics of Cuban healthcare system that continues to impress and produce enviable results. There are plenty of lessons to learn from Cubans in terms of proper healthcare organization with only one goal: to ensure a healthier future.
1. Cuba’s primary health care revolution: 30 years on. http://www.who.int/bulletin/volumes/86/5/08- 030508/en/. [Online] [Cited: February 24, 2018.] 2. Ley No. 41. Ley de la Salud Pública. http://www.parlamentocubano.cu/index.php option=com_content_iew=article&id=257:ley-no-41- salud ublica&catid=46:leyes&Itemid=79.[Online] [Cited: February 24, 2018.] 3. Gray, Bradford H. For-Profit Enterprise in Health Care. s.l. : Washington (DC): National Academies Press (US), 1986. 4. Eradication of poliomyelitis in Cuba: a historical perspective. P, Más Lago. s.l. : Bull World Health Organ, 1999, Vol. 77(8). 681-7. 5. Caring for Them from Birth to Deat. C, Perez. s.l. : Lanham, MD: Rowman & Littlefield Publishers, 2008. 6. Health for all: a dream realized in Cuba. CW, Keck. s.l. : Medical and Health Annual. Chicago, IL: Encyclopaedia Britannica Inc., 1994. 357–362. 7. he Cuban health system: responsiveness to changing population needs and demands. SM, Santana. s.l. : World Dev, 1987, Vol. 15(1). 113–125. 8. The Curious Case of Cuba. Keck, C. William. s.l. : Am J Public Health, 2012, Vol. 102(8). e13–e22. 9. WHO VALIDATES ELIMINATION OF MOTHER-TO-CHILD TRANSMISSION OF HIV AND SYPHILIS IN CUBA. s.l. : Saudi Med J, 2015, Vol. 36(8). 1018-9.
In spite of the U.S. embargo and due to the nature of its economic model being less market oriented than its counterparts and more focused on research for the bettering of the quality of life, Cuba has been able to established a strong and vibrant medical research and biotechnology industry with 1.8 scientists per 1000 inhabitants equal to that in the EU.
In an attempt to meeting internal demand for controlling and treating chronic diseases the biotechnology industry created the West Havana Scientific Pole in the early 1980s that developed informal and innovative scientific practices that became known for being one of the most advanced globally in establishing and developing a sophisticated and robust indigenous bio-pharmaceutical industry focused on human and veterinary vaccines, bioproducts, medicines, monoclonal antibodies, generics and alternative medicines as well as innovative diagnostic means.
Once described as “Cuba’s billion dollar gamble”, the Havana’s Western Scientific Pole is now includes over 40 scientific institutions and R&D facilities with over 900 international patents for new drugs and treatments and employs more than 30,000 workers. Currently, 11 vaccines and more than 40 therapeutic biological compounds as well as immunodiagnosis are produced in Cuba. Moreover, at present Cuba has 90 new products being investigated in clinical trials while f 91 products being investigated in more than 60 clinical trials.
It is also one of only four countries to have been accredited by the World Health Organisation for the production of Hepatitis B vaccines.
Developed by the Center for Genetic Engineering and Biotechnology (CIGB) in 2007 Heberprot-P is an innovative Cuban product with EGF as the main ingredient given to patients suffering from non healing and non responding diabetic ulcers. Due to its ability to stimulate cell proliferation and tissue healing Heberprot-P remains to be the only alternative treatment to amputation for diabetic foot ulcers. About 160,000 diabetic foot ulcer patient have been treated with Heberprot-P with successfully reducing the the risk of amputation by 77%.
CimaVax-EGF vaccine was devised by researchers from the Center of Immunoassay and the Center for Molecular Immunology (CIM) over a period of 25 years. CimaVax is the first world non small cell lung cancer vaccine that works by by stimulating the immune system to produce antibodies that specifically target and bind with epidermal growth factor (EGF) preventing the cancer from spreading throughout the body.CimaVax-EGF is not a preventive vaccine, rather it acts by restraining the growth and division of cancer cells slowing down initiating an immune response to release antibodies to fight the cause of tumor growth
A second non small cell lung cancer developed by enter of Immunoassay and the Center for Molecular Immunology (CIM), Racotumomab (also known as Vaxira) is a therapeutic vaccine that works on a molecule level by inducing a cellular and humoral immune response in tumors tissues by blocking the tumor growth, slowing down it’s development and hence increasing patient’s’ life expectancy and improving quality of life.
Nimotuzumab (CIMAher), also developed Center of Molecular Immunology, is a humanized anti-EGFR IgG1 therapeutic monoclonal antibody and used for the treatment of squamous cell of head and neck cancers, glioma and nasopharyngeal cancers. Nimotuzumab is used as either as monotherapy or in combination with radiation and / or chemotherapy. Presently research continues to determine if Nimotuzumab can be used for the treatment of other types of cancers.
Developed by the Center for Genetic Engineering and Biotechnology (CIGB), Heberferon is the first non melanoma skin cancer treatment at the complex and advanced stages. Heberferon is an immunostimulant in which Interferon alpha 2b and gamma recombinants are combined to stimulates the immune system into a response against tumor inhibiting the growth of the tumour while reducing or eliminating lesions without the need for surgery.
Cuban meningococcal BC vaccine (VA-MENGOC-BC®) was developed by the Finlay Institute in Havana due to a meningococcal outbreak in the 1980s. The first of its type, VA-MENGOC-BC is a bivalent vaccine composed of meningococcal B outer membrane vesicles and meningococcal C capsular polysaccharide. This vaccine has proven to be very effective with very high safety profile
Although meningitis and pneumonia have been almost erased in the developed world these diseases remain highly problematic in the developing world due the high cost of the vaccine. Cuban researchers at the University of Havana in conjunction with researchers at the university of Ottawa (Canada) have developed the first synthetically produced antigen. Quimi hib Vaccine works by producing antibodies that resist infection from bacteria that causes pneumonia and meningitis in a breakthrough aimed at lowering the cost of immunising children in poorer countries is considered to be safer and purer than vaccines developed from live bacterium or virus.
A lifetime risk for a diabetic ulcer in patients suffering from diabetes type 1 or 2 is approximated to 25%, meaning that every fourth person with diabetes will develop diabetic ulcer (1) . Diabetic foot ulcers represent a medically significant disease complication, with a high incidence of morbidity and mortality in the modern world. Risks for the development of this serious condition are well established and include the loss of sensation as a consequence of diabetes induced neuropathy, previous occurrences ulcers or amputations, infection, trauma, and the consequences of chronic ischemia due to poor peripheral vascularization (2) . Contemporary treatment options for diabetic foot ulcers are still limited, directly resulting in amputation being the frequent therapeutic solution for the majority of severe ulcers. Recent advancements in medical science regarding treatment for diabetes and its' complications have shown that the use of epidermal growth factor (Heberprot-P) as the treatment of diabetic foot ulcer may lead to the complete wound healing, significantly reducing the risk of amputation.
Most Recent Scientific Data
It is now well recognized that diabetic patients have decreased amounts of epidermal growth factor (EGF) in tissues which directly results in wound healing impairment and subsequently to the increased risk of amputation. EGF is directly responsible for the growth of epithelial and subepithelial tissues, and promotes reparation processes of tissues that are damaged (3) .
Heberprot-P is an innovative recombinant human EGF developed for acceleration of healing process of deep and complex ulcers in both neuropathic and ischemic types of diabetic ulcers. It currently represents the unique treatment for the most complicated diabetic wounds which are linked with a high risk for amputation. Efficacy and safety of Heberprot-P have been investigated in numerous clinical trials worldwide, with results demonstrating full wound healing, reduction of ulcer recurrence, as well as a reduction in amputations rates. Heberprot-P has proven to be a safe and well-tolerated treatment option for the treatment of severe diabetic ulcers, with adverse events mostly consisted of mild and transitory local reactions (4) .
A recent extensive meta-analysis involving 2365 participants conducted for the purpose of investigating the effects of growth factors on the healing of diabetic ulcers concluded that growth factors (EGF among them) may lead to complete healing of diabetic foot ulcers (5) . Another meta-analysis and systematic review of literature data conducted on 294 patients also identified favorable patient outcomes following treatment with recombinant human EGF (6) . Efficacy of Hebeprot-P was recently investigated in a clinical study involving patients having extensive, full-thickness lower extremity ulcers. Administration of Heberprot-P resulted in complete granulation followed by complete wound closure in 94% of patients. After one year follow-up, only one patient had a relapse of foot ulcer (7) . The interesting mechanistic of healing effects of EGF (Hebeprot-P) has also been investigated recently. It was recognized that diabetic patients have elevated oxidative stress and low antioxidant reserves. Application of EGF resulted in significant reduction of oxidative stress and elevation in antioxidant reserves, directly returning balance to oxidative processes in diabetic patients (8) .
The safety profile was recently investigated in the longitudinal, multicenter, post-marketing surveillance study which included 260 patients. The results were in line with the already known safety profile of Heberprot-P. Most frequently reported adverse events were mild and reversible in nature, including localized Burning sensation and pain at the injection site, as well as systemic reactions such as chills and shivering (9) . In conclusion, the benefits of Heberprot-P significantly outweigh the risks of this therapy. Heberprot-P can be safely administered to diabetic patients without the risk of serious and irreversible adverse reactions.
Advancements in Treatment
The recognized therapeutic potential of Heberprot-P prompted another clinical trial that would assess the efficacy and safety of Heberprot-P in patients with high-grade diabetic ulcers. The study is conducted at the eminent Dasman Diabetes Institute in Kuwait. Results of numerous studies are promising and justify the further testing of Heberprot-P, a unique and first-in-class therapeutic option for complicated diabetic ulcers. This provides the opportunity to further evaluate beneficial potentials of Heberprot-P and addresses the unmet medical need of introducing an effective therapeutic modality in the treatment of complex and serious diabetic foot ulcers.
The Unmet Need
An accumulated body of scientific evidence clearly indicates that the use of growth factors (especially recombinant human EGF) is beneficial for complicated diabetic foot ulcers with very high success rates. Current antimicrobial treatments, as well as the broad spectrum of different procedures involving surgery and drugs, have failed to decrease amputation rates and successfully treat this serious complication of diabetes. Heberprot-P is a registered treatment for diabetic foot ulcers in dozens of countries worldwide, and it has been successfully used in over 100.000 patients suffering from complex ulcers.
The need for an effective treatment clearly remains, and Heberprot-P has demonstrated to be an effective solution where standard therapeutic options fail. According to the most current data published by the Center for Disease Control (CDC), more than 100 million Americans have diabetes or prediabetes (10) , which represents a high-risk burden for diabetic foot ulcers, considering that every fourth diabetic patient may develop this condition. Complete regression of the most complicated ischemic diabetic
ulcers has been achieved in a significant portion of diabetic patients. Heberprot-P would address therapeutic needs of patients, in which amputation represents the only treatment option.
1. Comprehensive foot examination and risk assessment: a report of the task force of the foot care interest group of the American Diabetes Association, with endorsement by the American Association of Clinical Endocrinologists. Boulton AJ, Armstrong DG, Albert SF, Frykberg RG, Hellman R, Kirkman MS, Lavery LA, Lemaster JW, Mills JL Sr, Mueller MJ, Sheehan P, Wukich DK, American Diabetes Association, American Association of Clinical Endocrinologists. s.l. : Diabetes Care, 2008, Vol. 31(8). 1679.
2. Diabetes in America, 2nd Edition. National, Diabetes Data Group. s.l. : National Institutes of Health, Washington, D.C. 409.
3. Epidermal growth factor in the treatment of diabetic foot ulcers: an update. Tiaka EK, Papanas N, Manolakis AC, Georgiadis GS. s.l. : Perspect Vasc Surg Endovasc Ther., 2012, Vol. 24(1). 37-44. 4. Heberprot-P: A Novel Product for Treating Advanced Diabetic Foot Ulcer. Jorge Berlanga DVM MS PhD, José I. Fernández MD, Ernesto López MS, Pedro A. López MD PhD, Amaurys del Río MD, Carmen Valenzuela MS, Julio Baldomero MD, Verena Muzio MD PhD, Manuel Raíces PhD, Ricardo Silva PhD, Boris E. Acevedo MD PhD, Luis Herrera MD PhD. s.l. : MEDICC Rev, 2013, Vol. 15(1). 11.
6. Efficacy of Topical Recombinant Human Epidermal Growth Factor for Treatment of Diabetic Foot Ulcer: A Systematic Review and Meta-Analysis. Yang S, Geng Z, Ma K, Sun X, Fu X. s.l. : Int J Low Extrem Wounds, 2016, Vol. 15(2). 120-5.
7. Efficacy of intralesional recombinant human epidermal growth factor in chronic diabetic foot ulcers. Dumantepe M, Fazliogullari O, Seren M, Uyar I, Basar F. s.l. : Growth Factors, 2015, Vol. 33(2). 128-32.
8. Healing enhancement of diabetic wounds by locally infiltrated epidermal growth factor is associated with systemic oxidative stress reduction. Ojalvo AG, Acosta JB, Marí YM, Mayola MF, Pérez CV, Gutiérrez WS, Marichal II, Seijas EÁ, Kautzman AM, Pacheco AE, Armstrong DG. s.l. : Int Wound J, 2017, Vol. 14(1). 214-225.
9. Characterization of adverse events during the treatment with heberprot-p® in four Cuban provinces. Alina Ramona Alvarez Crespo, Liuba Alonso Carbonell, Isis Belkis Yara Alos, Ana Julia Garcia Milian, María Acelia Marrero Miragaya. s.l. : Horizonte Sanitario, 2017, Vol. 17.
10. National Center for Chronic Disease Prevention and Health Promotion. National Diabetes Statistics Report, 2017. s.l. : Center for Disease Control, 2017.
CubaHeal Medical is a global organization specialized in facilitating medical treatments, medical education, in addition to patient and student care in the Republic of Cuba. CubaHeal is a loyal supporter of the Republic of Cuba, the Cuban people, the Cuban revolution, and the Cuban revolutionary leadership.