India, which shares 17% of global population, has finally had its first dedicated policy on making treatment of rare diseases accessible and affordable.
by Dr. Dipanjana Datta
While rare diseases are called so because of their low prevalence, victims of these diseases and people around them do have their worlds turned upside down. The global focus and financial investment on rare diseases are thin, and policy measures have been achingly missing.
But things are indeed changing significantly for the better, and countries are increasingly recognising the need to address the challenge. For instance, India, which shares 17% of global population, has finally had its first dedicated policy on making treatment of rare diseases accessible and affordable. Having said that the global policies around the world is highly dependent on the success of medical sciences for such diseases.
The Gaucher Disease
While rare diseases and their cure are highly difficult to understand and discover, from a research view point, the rarity of rare disease provides scientist and medical researchers really unique avenues of understanding human bioscience. So much so, any success on these front will potentially have a far-reaching impact on other disease areas. Gaucher is one such rare disease which is witnessing much interesting work being done.
Being an inherited metabolic lysosomal storage disease (LSD), Gaucher is caused by mutations in both the copies of glucocerebrosidase (GBA1) gene, resulting in the deficiency of β-glucosidase enzyme. The enzyme deficiency causes the accumulation of toxic materials in body’s cells, affecting different body parts, including central nervous system, skin, heart and skeleton and so on. There are around 50 types of known LSDs, with Gaucher being the most common LSD in the world.
Major Progress in Past Century
Historically, there has been tremendous progress in identification of the disease and its subtypes as well as in discovering treatment regimen. The first medical presentation of the disease was recorded by French medical student Philippe Charles-Ernest Gaucher over a century and three decades ago. Philippe Gaucher in his medical thesis first described unusual cells appearing in one of his 34-year-old female patient who had presented with an enlarged spleen. It was only in 1901 that the disease was identified as a hereditary disorder.
However, it was the seminal work of Dr. Roscoe Brady and his team which led to major breakthroughs in the understanding and treatment of the disease. Many other researchers around the globe contributed to the subject, which has benefit not only Gaucher disease but also other lysosomal storage disorders.
Consequently, over 300 different GBA1 mutations have been identified to date. Largely categorised as types 1, 2, 3, perinatal lethal and cardiovascular disease the diagnosis, differentiation, and treatment of Gaucher disease was established. The research in the domain expanded our understanding of genotype complexities of the disease and our knowledge of full spectrum phenotypic manifestations also evolved. There has been crucial research in the areas of Gaucher disease association with Parkinsonism and malignancies. The collective efforts have also led to the advances in biochemistry as well as of the conceptualisation and development of enzyme replacement therapy.
The Current State & Way Forward in Medical Research
Medical research has taken major strides in determining better treatment methods for the disease, including enzyme replacement therapy (ERT) and substrate reduction therapy (SRT).
There has been significant development of drugs in the past decade or two. ERT happens to be one of the most effective treatment methods for the Gaucher disease. It has been greatly effective in reducing the risks of avascular osteonecrosis and in turning around hepatosplenomegaly, osteopenia, and cytopenia, especially in children and young adults. The therapy is so effective that new generation of Gaucher disease patients don’t have to undergo splenectomy.
Presently, SRT is being prescribed to only some patients all over the world. Other domains which have shown greater progress as a stronger solution include gene therapy prospects, pharmacological chaperones as therapeutic approach, histone deacetylase inhibitors, and others. Furthermore, new research tools such as the mouse models and cell-based models provide exciting avenues to find a better effective treatment of Gaucher disease.
The Essential Policy Connect
With the second highest population in the world, even rare diseases gain significant to large size in India. Furthermore, India is majorly an endogamous population, as marriage in India takes place within communities. Even if it is not consanguineous, we are majorly an endogamous population, and so there is a risk of higher incidence of rare diseases. Around 2008-09, WHO had earlier stated that India has a higher risk of non-communicable diseases than communicable diseases, which we are experiencing increasingly. Therefore, it becomes essential that India must take proactive and leading policy decisions in sync with the global advances in medical sciences especially in rare diseases. With regards to Gaucher disease, the recent decades have witnessed tremendous advancements. However, the cost of the highly complex treatment regimen and therapies is far beyond the means of the common man. Therefore, the following are some of the essential measures that need to be initiated aggressively in order to establish ourselves as Atmanirbhar or self-reliant in the space of medical research and treatment Gaucher disease.
Back Indian Research in Rare Disease.
To have an effective therapy designed for the Indian population, national medical research needs to be aggressively promoted and supported with finances, resources, and infrastructure. While breakthroughs and innovations in rare diseases may be difficult to find, but they are more likely to come out with game changing treatment pathways for not only the disease itself but for other complex ailments.
Map Epidemiology
Presently, we are by and large considering International data and extrapolating it to Indian population size. There is still a lot of uncertainty on the exact prevalence and spread of Gaucher disease in India. Epidemiological mapping of Gaucher cases will guide policy making and will help in facilitating aid and intervention to the right people. It will also give important insights to medical communities and pharma companies to conduct research and produce ERTs and SRTs adequately.
Orphan Drug Policy.
While Rare Diseases Policy is indeed a major step for India towards embracing certain challenges in the domain, it is the Orphan Drug Policy which can strengthen the fight against these diseases by addressing the poor economic potential challenges related to treatment of rare diseases. The policy should be empowered with tax incentives and clinical research subsidies,enhanced IPR protection, and other measures by the Government.
Prenatal Diagnosis & Preconception Counselling.
India does not have an impressive track record in prenatal diagnosis and preconception counselling majorly due to lack of public awareness and education and partially due to affordability and accessibility of adequate services. By promoting preconception and prenatal genetic counselling, informed reproductive decision making can be encouraged in couples identified at increased risk of bearing children with genetic conditions or anomalies.
Activate Insurance Support.
More innovative models are needed from the public and private Insurance sector in embracing rare disease patients and in providing them with the financial support, say by means of EMIs.
Better Diagnosis.
When making a diagnosis, doctors must rule out Gaucher disease as well and not just other diseases. This can help in early diagnosis and treatments. To do this, doctors must take patient histories more seriously and check for all red flags.
As per a recent study published in the reputed journal Nature, the disease prevalence “in the non-Ashkenazy Jewish population is estimated at 1:40,000–100,000 subjects, whereas in Ashkenazi Jewish is 1:500–1000.”
A possibility of a higher number in India cannot be ruled out without on-ground research and epidemiological mapping of rare diseases. Meanwhile, most of these patients are undiagnosed and without treatment, with high chances of facing some societal stigma. It is important that innovative policy and technological measures are initiated to make treatment and right guidance accessible to the patients and their families.
Dr. Dipanjana Datta, Genetic Counsellor and West Bengal State Coordinator, Organization For Rare Diseases India (ORDI).
