IMS-BHU researchers identify novel drug target for treating Alzheimer’s disease

Researchers at the Institute of Medical Sciences, Banaras Hindu University (IMS-BHU) have identified RhoA as a novel drug target in the treatment of Alzheimer’s disease. The study has been published in the FASEB Journal.

Dr Debabrata Dash, professor and head, department of biochemistry, IMS-BHU, said, “We have discovered a novel drug target of amyloid beta toxicity and Alzheimer’s disease in platelet model. We have found that amyloid beta exercises its activity on a cell through activation of a small GTP-binding protein known as RhoA. When we inhibit RhoA activity by employing pharmacological inhibitors, the toxic effects of amyloid beta are prevented. This information would have significant implications in drug development against Alzheimer’s disease.”

Alzheimer’s disease is the most common cause of cognitive decline and memory loss in the elderly. Although local deposit of a small peptide called ‘amyloid-beta’ is known to be responsible for Alzheimer pathology, the underlying molecular mechanism remains largely obscure. This is the reason why there is no effective therapy against this highly debilitating condition.

Platelets are blood cells that are responsible for stoppage of bleeding at the site of injury. Interestingly, platelets are a major source of amyloid-precursor protein in blood.

Dr Dash and co-workers (Vijay Sonkar and Paresh Kulkarni) at Banaras Hindu University have identified target molecules of amyloid-beta in cells using platelets as peripheral model of neurons.

Their study showed that amyloid-beta was able to strongly stimulate platelets leading to aggregate formation. Intravenous administration of the peptide in mouse accelerated thrombus formation in pulmonary vessels.

The effect of amyloid-beta on platelets was found to be mediated through activation of RhoA, a small GTP-binding protein responsible for cytoskeletal reorganization in cells, and that inhibition of RhoA by a specific pharmacological agent reversed the effects of amyloid-beta on platelets.

In order to understand molecular underpinnings amyloid action, researchers went further to demonstrate phosphorylation of downstream effectors of RhoA, namely MYPT1 and myosin light chain, when the cells were exposed to amyloid-beta.

According to the researchers, patients of Alzheimer’s also have clotting abnormalities, which could be explained by amyloid-beta-induced activation of platelets.

“The findings of this study thus identify RhoA as a novel drug target in the treatment of Alzheimer’s disease, and unravel the possible cause of clotting abnormalities seen in these patients,” said Dr Dash.

Sourrce: India Medical Times

 


ENT specialist treats burn injury patient, fined Rs 4 lakh for negligence

The National Consumer Disputes Redressal Commission (NCDRC), while setting aside an order of the Bihar State Consumer Disputes Redressal Commission, held a doctor guilty of medical negligence and directed him to pay a compensation of Rs 4 lakh to a man who lost his hand due to his treatment.

NCDRC president D K Jain and members Vineeta Rai and Vinay Kumar, while hearing the revision petition, held that the Bihar State Commission erred in not correctly assessing and appreciating the evidence before them and erroneously concluding that there was no medical negligence.

The aggrieved, Jai Prakash Mehta, a resident of Bihar sustained serious burn injuries on his right arm due to electric shock while working on the electrification of a railway line as a contract labourer on June 26, 1998. He was taken to Dr B N Rai, an ENT specialist, under whom the aggrieved underwent treatment for over two weeks following which there was further deterioration of the burn injuries in his right arm.

Dr Rai then referred him to the Institute of Medical Sciences and Sir Sunderlal Hospital, Banaras Hindu University (BHU), Varanasi, where he was informed that gangrene had set in which could not be reversed and his arm had to be amputated.

Distressed by the medical negligence on the part of Dr Rai, which had very adverse and serious financial and emotional consequences for him, Jai Prakash approached the District Consumer Disputes Redressal Forum, Rohtas, Sasaram on grounds of medical negligence and deficiency in service and requested for compensation.

The District Forum dismissed the complaint on the grounds that there was no credible evidence to prove that there was any medical negligence on the part of the doctor and further that he was not a ‘consumer’ since no fees were taken from him by the doctor. Jai Prakash filed another appeal before the State Commission, which in its order upheld the findings of the District Forum.

Jai Prakash then filed a revision petition in the NCDRC, challenging the order of the Bihar State Commission.

The NCDRC in its observation stated, “The finding of the State Commission that no medical evidence was produced, including expert opinion, to prove that the medicines prescribed were not effective or incorrect is not tenable because this is a case of res ipsa loquitur, wherein the facts speak for themselves. If Petitioner had been properly treated for his serious burn injuries and referred in time to an appropriate health facility by the doctor, then gangrene and consequent loss of his right arm could have well been avoided.”

It noted, “Clearly the doctor, who was an ENT specialist, did not have the professional competence and skills to treat the patient for burn injuries and instead misled him by assuring that the medicines mainly in the form of first aid treatment would lead to his recovery. It is clear that the Petitioner got wet gangrene because of the burn injuries which were not properly and adequately medically treated for over two weeks by the doctor.”

Source: India Medical Times