Understanding pathophysiology of GNE myopathy and current progress towards drug development
J Biosci. 2024;49:29.ABSTRACTGNE myopathy is a rare genetic neuromuscular disease that is caused due to mutations in the GNE gene responsible for sialic acid biosynthesis. Foot drop is the most common initial symptom observed in GNE myopathy patients. There is slow progressive muscle weakness in the lower and upper extremities while the quadriceps muscles are usually spared. The exact pathophysiology of the disease is unknown. Besides sialic acid biosynthesis, recent studies suggest either direct or indirect involvement of GNE in other cellular functions such as protein aggregation, apoptosis, ER stress, cell migration, HS...
Source: Journal of Biosciences - February 22, 2024 Category: Biomedical Science Authors: Fluencephila Mashangva Shagun Singh Jyoti Oswalia Ranjana Arya Source Type: research

Orphan drug development: Challenges, regulation, and success stories
J Biosci. 2024;49:30.ABSTRACTRare diseases, also known as orphan diseases, are diseases with low occurrence in the population. Developing orphan drugs is challenging because of inadequate financial and scientific resources and insufficient subjects to run clinical trials. With advances in genome sequencing technologies, emergence of cell and gene therapies, and the latest developments in regulatory pathways, some orphan drugs that have curative potential have been approved. In India, due to its large population and resource crunch, developing orphan drugs is phenomenally challenging. After adopting the Orphan Drug Act, the...
Source: Journal of Biosciences - February 22, 2024 Category: Biomedical Science Authors: Narendra Chirmule Huije Feng Esha Cyril Vihang Vivek Ghalsasi Mohua Chakraborty Choudhury Source Type: research

Lessons from the Rare Diseases Registry and Analytics Platform framework for development of a national rare diseases registry for India
This article explores the development of a comprehensive national RD registry for India, informed by insights gained through interactions with experts from India and the Asia-Pacific Economic Cooperation (APEC) region. The social and technological challenges involved in creating and maintaining a national RDs registry are highlighted. Moreover, the roles and responsibilities of different stakeholders are discussed. Additionally, the RD-RAP (Registry and Analytics Platform) framework is also discussed, which is an analytics-based RD registry model with multi-stakeholder end-user utility. Although developed for the APEC regi...
Source: Journal of Biosciences - February 22, 2024 Category: Biomedical Science Authors: Pragya Chaube Avani Lankapalli Mohua Chakraborty Choudhury Source Type: research

Decoding the mitochondria without a code: mechanistic insights into mitochondrial DNA depletion syndromes
J Biosci. 2024;49:32.ABSTRACTMitochondrial DNA depletion syndromes (MDS) encompass a wide spectrum of rare genetic disorders caused by severe reduction in mitochondrial DNA (mtDNA), and exhibit heterogenous phenotypes classified as myopathic, encephalomyopathic, hepatocerebral, and neurogastrointestinal. Prognosis for such a spectrum of diseases is poor and is majorly dependent on symptomatic treatment and nutritional supplementation. Understanding the mechanistic aspect of mtDNA depletion can help bring forth a new era of medicine, moving beyond symptomatic treatment and focusing more on organelle-targeted therapies. In t...
Source: Journal of Biosciences - February 22, 2024 Category: Biomedical Science Authors: Ritoprova Sen Cuckoo Teresa Jetto Ravi Manjithaya Source Type: research

mRNA biotherapeutics landscape for rare genetic disorders
J Biosci. 2024;49:33.ABSTRACTThe medical emergency of COVID-19 brought to the forefront mRNA vaccine technology where the mRNA vaccine candidates mRNA-1273 and BNT162b2 displayed superlative and more than 90% efficacy in protecting against SARS-CoV2 infections. Rare genetic disorders are rare individually, but collectively they are common and represent a medical emergency. In mRNA biotherapeutic technology, administration of a therapeutic protein-encoding mRNA-nanoparticle formulation allows for in vivo production of therapeutic proteins to functionally complement the protein functions lacking in rare disease patients. The...
Source: Journal of Biosciences - February 22, 2024 Category: Biomedical Science Authors: V Rajesh Iyer Praveen P Bhagyashree D Kaduskar Shivranjani C Moharir Rakesh K Mishra Source Type: research

Rare genetic diseases in India: Steps toward a nationwide mission program
J Biosci. 2024;49:34.ABSTRACTRare genetic diseases are rare by themselves with prevalence of 1 in 25,000, but collectively they are a significant cause of morbidity and mortality. Till date, collectively there are more than 9,000 rare diseases documented, which impose a devastating impact on patients, their families, and the healthcare system, including enormous societal burden. Obtaining a conclusive diagnosis for a patient with a rare genetic disease can be long and gruelling. For some patients it takes months or years to receive a definite diagnosis, and around 50% of the patients remain undiagnosed even with expert cli...
Source: Journal of Biosciences - February 22, 2024 Category: Biomedical Science Authors: Anjana Kar Sundaravadivel P Ashwin Dalal Source Type: research

Are all VapC toxins of < em > Mycobacterium tuberculosis < /em > endowed with enigmatic RNase activity?
J Biosci. 2024;49:35.ABSTRACTMycobacterium tuberculosis (M. tb) employs an extensive network of more than 90 toxin-antitoxin systems, and among them, VapC toxins are the most abundant. While most VapCs function as classical RNases with toxic effects, a significant number of them do not exhibit toxicity. However, these non-toxic VapCs may retain specific RNA binding abilities as seen in case of VapC16, leading to ribosome stalling at specific codons and reprofiling M. tb's proteome to aid in the bacterium's survival under different stressful conditions within the host. Here, we challenge the conventional classification of a...
Source: Journal of Biosciences - February 22, 2024 Category: Biomedical Science Authors: Sheeba Zarin Anwar Alam Seyed Ehtesham Hasnain Nasreen Zafar Ehtesham Source Type: research

Spinal muscular atrophy: Molecular mechanism of pathogenesis, diagnosis, therapeutics, and clinical trials in the Indian context
J Biosci. 2024;49:36.ABSTRACTSpinal muscular atrophy (SMA) is a neuromuscular, rare genetic disorder caused due to loss-of-function mutations in the survival motor neuron-1 (SMN1) gene, leading to deficiency of the SMN protein. The severity of the disease phenotype is inversely proportional to the copy number of another gene, SMN2, that differs from SMN1 by a few nucleotides. The current diagnostic methods for SMA include symptom-based diagnosis, biochemical methods like detection of serum creatine kinase, and molecular detection of disease-causing mutations using polymerase chain reaction (PCR), multiplex ligation-depende...
Source: Journal of Biosciences - February 22, 2024 Category: Biomedical Science Authors: Ashutosh Aasdev Sreelekshmi R S V Rajesh Iyer Shivranjani C Moharir Source Type: research

Recent developments in gene therapy research in India
J Biosci. 2024;49:37.ABSTRACTInherited genetic disorders are progressive in nature and lead to organ dysfunction or death in severe cases. At present, there are no permanent treatment options for >95% of inherited disorders. Different modes of inheritance, type of gene(s) involved, and population-based variations add further complexity to finding suitable cures for approximately 400 million patients worldwide. Gene therapy is a very promising molecular technique for the treatment of rare genetic disorders. Gene therapy functions on the basis of restoration, replacement, inhibition, and, most recently, editing of gene(s)...
Source: Journal of Biosciences - February 22, 2024 Category: Biomedical Science Authors: Ruchita Selot Arkasubhra Ghosh Source Type: research

Enhancing access to treatment for Gaucher disease in India: The need for indigenous manufacturing
This article aims to address this issue by advocating for the establishment of indigenous manufacturing capabilities for GD medicines in India. Through an examination of the current landscape of GD treatment, including the availability, affordability, and challenges associated with imported medications, this article highlights the urgent need for localized production. By focusing on the potential benefits of indigenous manufacturing, such as reduced costs, increased accessibility, and enhanced availability, this research aims to provide insights and recommendations to policymakers, healthcare professionals, and relevant st...
Source: Journal of Biosciences - February 22, 2024 Category: Biomedical Science Authors: Nidhi Patel Heta Pandya Ganesh Sangle Mohua Chakraborty Choudhury Source Type: research

Current status of research in rare genetic disorders and drug discovery in India
J Biosci. 2024;49:39.ABSTRACTThe major health agenda of India so far has prioritized infectious diseases and public health. Given the socioeconomic conditions and poverty, a large fraction of the Indian population is exposed to infections from different pathogens, most notably enteric, parasitic, mycobacterial, and viral. In recent years, however, there has been a decline in the spread of these diseases with better surveillance, availability of therapy, improvement of socioeconomic conditions, and education. It is now being realized that non-communicable diseases are reaching epidemic proportions in India and there is a gr...
Source: Journal of Biosciences - February 22, 2024 Category: Biomedical Science Authors: Alok Bhattacharya Sudha Bhattacharya Rakesh Mishra Source Type: research

The rare genetic disease research landscape in India
J Biosci. 2024;49:40.ABSTRACTI am delighted to see this special issue on 'The Rare Genetic Disease Research Landscape in India'' by the Journal of Biosciences, published by the Indian Academy of Sciences in collaboration with Springer Nature. It is the first time that a mainstream biology journal has decided to publish a whole issue on rare genetic disorders. I congratulate the editorial board of the Journal of Biosciences for their timely support to encourage research in this area. I also believe that this issue will increase awareness about rare genetic diseases research and encourage many in India to enter the field.PMI...
Source: Journal of Biosciences - February 22, 2024 Category: Biomedical Science Authors: Vinod K Paul Source Type: research

Patient's perspective about research landscape for rare diseases in India
J Biosci. 2024;49:25.ABSTRACTI am writing this piece as the parent of a son diagnosed with Duchenne muscular dystrophy, a severely debilitating disease that not only impairs skeletal muscles of the limbs but is also life-threatening due to progressive weakening of the cardiac and diaphragm muscles. I have traversed the harrowing diagnostic, treatment, and management odyssey of a typical rare disease (RD) patient in India.PMID:38383970 (Source: Journal of Biosciences)
Source: Journal of Biosciences - February 22, 2024 Category: Biomedical Science Authors: Ambrish Kapadia Source Type: research

Challenges and opportunities for discovering the biology of rare genetic diseases of the brain
J Biosci. 2024;49:26.ABSTRACTDiseases of the human nervous system are an important cause of morbidity and mortality worldwide. These disorders arise out of multiple aetiologies of which rare genetic mutations in genes vital to nervous system development and function are an important cause. The diagnosis of such rare disorders is challenging due to the close overlap of clinical presentations with other diseases that are not of genetic origin. Further, understanding the mechanisms by which mutations lead to altered brain structure and function is also challenging, given that the brain is not readily accessible for tissue bio...
Source: Journal of Biosciences - February 22, 2024 Category: Biomedical Science Authors: Padinjat Raghu Yojet Sharma Aswathy Bhuvanendran Nair Suseela Devi Harini Krishnan Source Type: research

Non-viral delivery of nucleic acid for treatment of rare diseases of the muscle
J Biosci. 2024;49:27.ABSTRACTRare muscular disorders (RMDs) are disorders that affect a small percentage of the population. The disorders which are attributed to genetic mutations often manifest in the form of progressive weakness and atrophy of skeletal and heart muscles. RMDs includes disorders such as Duchenne muscular dystrophy (DMD), GNE myopathy, spinal muscular atrophy (SMA), limb girdle muscular dystrophy, and so on. Due to the infrequent occurrence of these disorders, development of therapeutic approaches elicits less attention compared with other more prevalent diseases. However, in recent times, improved underst...
Source: Journal of Biosciences - February 22, 2024 Category: Biomedical Science Authors: Divya Rao Munia Ganguli Source Type: research