Reinvigorating its efforts towards eradication of tuberculosis by 2025, the Maharashtra government has recently approved a proposal to supply free TB drugs to retail chemists in parts of the state which will ensure poor patients’ access to TB drugs smoothly.
On March 14, 2018 Directorate of Medical Education and Research (DMER) had written to Maharashtra Food and Drug Administration (FDA) informing them about the decision. DMER in the letter stated that the chemists with a valid licence will get TB drugs from the state government. They can store and distribute drugs to TB patients for free.
Lakhs of resource crunch TB patients visiting DOTS centres to get TB drugs will benefit from the initiative. All the medicines required to treat TB patients are available free of cost at DOTS centres under Revised National TB Control Program (RNTCP).
As of now certain chemists in Mumbai have been designated to get free TB drugs from the state government and supply them to patients. It will gradually be extended to parts of the state so that maximum patients benefit from the initiative, said Dr Sanjeev Kamble, state TB officer.
Talking about the criteria to identify the chemists for distribution of free TB drugs, Dr Kamble said “The chemists located in semi urban areas, urban areas reporting significant number of TB cases to the government will be designated for distribution of TB drugs to patients for free.”
Arjun Khadtare, joint commissioner, FDA confirming the DMER letter said “With this the chemists having valid licence can store and distribute free TB drugs to patients. The list of chemists who will get free TB drugs from the state government will be prepared by the state TB cell. We are ensuring strict implementation of Schedule H1 containing TB drugs at retail drug stores to make TB control programme more effective.”
As per Schedule H1, pharmacies are required to dispense anti TB drugs on prescription of a registered medical practitioner and maintain a separate register containing the name and address of the prescriber, the name of the patient, the name of the drug and the quantity supplied and such records shall be maintained for three years and be open for inspection.
TB was responsible for 1.7 million deaths in 2016, despite most cases being curable. India continues to have the highest number of TB cases in the world, stated the Global TB Report 2017 released by World Health Organization (WHO).
Low doses of a compound called romidepsin might help those on the autism spectrum overcome the social challenges that define their condition.
So far it has only been shown to be effective in mice, but the mechanisms behind the drug’s activity make it a promising candidate for an autism treatment in humans – the first of its kind.
Autism spectrum disorder (ASD) is an umbrella term for traits that interfere with the brain’s ability to process stimuli and negotiate social cues, often making communication difficult.
While there is no single gene that’s responsible for these characteristics, past research has found a number of genes do influence the disorder’s appearance. Some are inherited, while others seem to be the product of mutations early in life.
Researchers from the University at Buffalo in New York focussed their studies on a third way that genes can be changed – epigenetics.
Environmental factors can often trigger enzymes in the body to wrap up parts of the chromosome containing certain genes a little too tightly, effectively hiding them away. There is strong evidence suggesting a number of genes commonly associated with ASD are silenced by this overenthusiastic wrapping process.
What’s more, high levels of an enzyme called histone deacetylase, or HDAC2, observed in lab studies involving mice could be responsible for this process.
“In the autism model, HDAC2 is abnormally high, which makes the chromatin in the nucleus very tight, preventing genetic material from accessing the transcriptional machinery it needs to be expressed,” says senior author and molecular biologist Zhen Yan.
In other words, pumped up levels of HDAC2 could be locking away key genes, giving rise to some of ASD’s signature traits.
Inhibiting this enzyme could help the strands of DNA relax and let the genes do their job again, potentially restoring the brain’s ability to navigate social situations.
We already have a US government-approved drug that does this; a compound called romidepsin, currently used as a treatment for certain kinds of lymphoma.
Turning to a cancer drug wasn’t a mere stab in the dark, either.
“The extensive overlap in risk genes for autism and cancer, many of which are chromatin remodelling factors, supports the idea of repurposing epigenetic drugs used in cancer treatment as targeted treatments for autism,” says Yan.
To test whether the drug would indeed help alleviate ASD symptoms, the researchers used mice engineered with mutated versions of the Shank3 gene.
Previous research had already shown how changes to Shank3 were behind major differences in areas of the brain associated with socialisation.
More importantly, around 1 percent of ASD diagnoses are currently thought to be associated with Shank3 mutations. That might not sound like much, but given a condition as complex as autism it’s significant enough to be worth pursuing.
The team speculated that there had to be a link between the loss of Shank3 and the ramping up of HDAC2 in the nucleus.
Through a series of experiments designed to study the links between elevated HDAC2 levels and Shank3 mutations, the scientists teased out the biochemical steps to show how epigenetic changes were ultimately responsible for ASD’s social challenges in a number of individuals.
The best part is romidepsin successfully impeded HDAC2 and improved social skills in their mice models, suggesting there was a way to ease these challenges in humans.
“Autism involves the loss of so many genes,” says Yan. “To rescue the social deficits, a compound has to affect a number of genes that are involved in neuronal communication.”
Of course mice aren’t people, but since the mechanisms appear to be the same, there’s hope that the drug’s effects will be as well.
The fact it’s already FDA approved also suggests a treatment is tantalisingly on the horizon.
It’s important to keep in mind that there’s still plenty of research between this study and a publically available treatment.
Still, given there are currently no other treatments that come close to covering this ground, it’s hard not to get excited.
This research was published in Nature Neuroscience.
The Indian Council of Medical Research (ICMR) has issued draft consensus document for management of acute myeloid leukaemia (AML) to assist the doctors in making major clinical decisions encountered in managing their patients.
The consensus document provides details to the doctors about AML and its diagnosis, treatment, consolidation therapy in AML, management of elderly AML, prognostic factors in AML, guideline for management of acute promyelocytic leukaemia, treatment of granulocytic sarcoma, down syndrome & acute myeloid leukaemia and treatment of secondary acute myeloid leukaemia.
The initiative of the ICMR in this regard is significant as cases of AML are increasing in the country.
AML is characterized by clonal neoplastic proliferation of myeloid precursor cells in the marrow and arrest of their maturation. The replacement of marrow by leukaemic cells (blasts) leads to clinical features characterized by anaemia, thrombocytopenia and granulocytopenia with or without leukocytosis. The resultant accumulation of these non-functional blast cells prevents normal haematopoiesis, which if untreated will result in bone marrow failure and the death of the affected individual. Its annual incidence is 2-3 per 100,000. Incidence increases with age. It is less than 1per 100,000 under 30 years of age and 17 per 100,000 by 75 years. AML accounts for less than 10% of all leukaemia’s in children less than 10 years of age, and for 25-30% between 10 and 15 years. In adults, AML accounts for 80-90% of cases of acute leukaemia. The incidence is higher in males than in females. As per Delhi population based cancer registry AML constitutes about 3 per cent of all cancers with a median age of 32 years.
According to the document, symptoms of AML are results of bone marrow failure, tissue infiltration by leukaemic cells or may be due to circulating leukaemic cells. Patient usually presents with fatigue and abnormal bleeding. Weight loss, fever, night sweats may be present. Bone pain and testicular enlargement are due to extra medullary involvement by the leukaemic cells. Patient may have headache, vomiting, blurring of vision due to central nervous system involvement. On physical examination, pallor and features of thrombocytopenia like epistaxis, gingival bleed, petechial, ecchymotoic patches may be obvious findings. Patient may have organomegalyhepatosplenomegaly, Lymphadenopathy and gingival hypertrophy (usually in myelomonocytic and monocytic leukaemia or acute promyelocytic leukaemia). Rare features are skin involvement and arthritis.
ICMR has now asked the stakeholders to send their suggestions and comments to the Council by April 11, 2018.
Gene editing has the power to completely reshape our world.
It promises everything from fixing the genetic faults that lead to disease, to destroying disease-causing microbes, to improving the nutrition of the foods we eat and even resurrecting extinct species like the wooly mammoth – all largely thanks to the genetic editing tool CRISPR, which has both popularized this work and made it possible.
Now, researchers in Japan have developed a new gene editing technique that uses CRISPR alongside a DNA repair system to modify a single DNA base in the human genome, with what the team’s press release calls “absolute precision.”
The new technique, described in the journal Nature Communications, is known as known as MhAX, or Microhomology-Assisted eXcision.
This method came from a group of researchers working to better understand how single DNA mutations known as single nucleotide polymorphisms (SNPs) contribute to hereditary disease. To prove that a SNP causes disease, you need to compare genetically matched “twin” cells.
Yet because these twins differ by only a single SNP, they are incredibly difficult to make. MhAX came out of this difficulty, providing a new pathway to create twin cells.
To make these very precise edits, an SNP modification is first inserted alongside a fluorescent reporter gene that helps researchers to identify modified cells.
The researchers engineered a duplicate DNA sequence known as a microhomology (hence the technique’s name) on each side of the fluorescent gene, targeting sites for CRISPR to go in and cut DNA.
The researchers were then able to use a DNA repair system known as microhomology-mediated end joining (MMEJ) to remove the fluorescent gene. That left only the single-base edit, in the form of an SNP, behind.
The targeting and removal of this singular gene is truly exact.
“Our goal is to generate gene editing technologies which improve our understanding of disease mechanisms, and ultimately lead to therapies,” said Dr. Knut Woltjen, who led the research, in the press release.
“We’re confident that MhAX will have broad applicability in current human disease research, and beyond.”
CDSCO issues guidance document to streamline approval process for conducting BA/BE studies for export
The Central Drugs Standard Control Organisation (CDSCO) has come out with a comprehensive draft guidance document to streamline the approval process for conducting bioequivalence (BE) and bioavailability (BA) studies with human participants in India for export purposes.
BE studies are conducted to establish that two medicines, usually the original patented drug and a generic version, have the same biological equivalence, which means they work the same way and are interchangeable. The study is crucial for ensuring the safety and tolerability of generics against corresponding innovator drugs.
BA refers to the relative amount of drug from an administered dosage that enters the systemic circulation and the rate at which the drug appears in the systemic circulation.
The ministry of health and family welfare has recently amended the Drugs and Cosmetics Rules, 2017, to make BE studies compulsory for certain classes of generic drugs manufactured in India. However, those drug makers exporting to the US and the European Union are required to conduct these studies to gain marketing approval for those jurisdictions as BA and BE studies are recognised globally as an effective method to ensure therapeutic equivalence between a pharmaceutical equivalent test product and a reference drug.
According to industry sources, since the amendment to regulations, the number of pharmaceutical companies approaching the regulators to get approval for BE and BA studies has increased manifold.
The government has decided to come out with a draft guidance document to make the application process smooth-running. According to an official source, many applications get unnecessarily delayed in the absence of a detailed checklist. The new draft is expected to harmonise the submission process, shorten clearance time and help examiners reach quick and uniform decisions.
As per the guidance document, any firm that wants to conduct a BA and BE study should submit detailed study protocol, details of Ethics Committee registration, BA/BE Centre approval copy and other relevant documents mentioned in the checklist.
To obtain the CDSCO nod for the study of a new chemical entity not approved in India but cleared in other countries, an undertaking letter from the sponsor stating that he/she will provide complete medical care as well as compensation for the injury or death should be provided. Published reports of Pharmacokinetic and Pharmacodynamics studies carried out in healthy subjects demonstrating safety and tolerability of the molecule are also necessary.
For cytotoxic drugs, hormonal preparations, narcotic and psychotropic substances etc to be tested in healthy human subjects, a scientific justification with special emphasis on safety of subjects with a proper risk evaluation and mitigation strategy should be submitted. The guidance document also states that the firm should submit separate applications for different protocols along with requisite fee.