Monday, March 19, 2012

A blast from the past about Alzheimer's

The OPTIMA project has been going as long as I can remember but its founder (below) still seems to think vitamins are a way forward. There must be an awful lot of vitamin deficiency around if that is true

The fundamental problem with Alzheimer drug research is that it is almost entirely based on the ‘amyloid hypothesis’, a theory about what causes AD that appears increasingly invalid.

Amyloid is an insoluble toxic protein deposited between the nerve cells of the brain that has been shown to kill them. In 1991, scientists in London discovered that a mutated gene in the precursor protein to amyloid (beta-amyloid) caused a rare genetic form of AD. Since then, drug companies have considered that manipulating amyloid lies at the heart of dealing with AD.

But this puts all their eggs in one basket. Billions of pounds have been spent, and every single trial has failed. Some drugs made the symptoms of dementia worse.

Research should be geared towards intervening at an early stage. This is key to slowing down or stopping nerve cell death associated with AD. Once the nerve cells have died and the brain has shrunk, it’s too late.

I am the founding director of the Oxford Project to Investigate Memory and Ageing (OPTIMA), which studies the causes of dementia. Last year we recruited 270 elderly people with memory problems and gave them Vitamin B tablets – folic acid (800 micrograms), B12 (500 micrograms) and B6 (20 milligrams).

The supplements, which cost as little as 10p a day, were found to slow shrinkage of the brain by an average of 30 per cent a year – and slow the rate of cognitive decline – in people with high blood levels of homocysteine. Raised levels of this amino acid can increase the risk of developing AD three or four-fold.

By regulating homocysteine with B vitamins, we showed for the first time it is possible to slow the progress of the disease, if you start early. More trials are needed to test whether continued treatment can delay its progress indefinitely, but B vitamins have been shown to be as good clinically as Aricept – and better in that they slow the disease progression rather than ease the symptoms.

There is no way of knowing who is predisposed to AD, apart from extremely rare familial forms of AD.

But those with memory problems should have their homocysteine measured and be started on B vitamins, under medical guidance. Normal dietary intake isn’t enough. One (200ml) glass of semi-skimmed milk contains 2.5 micrograms of B12, and most manage to eat five micrograms a day. But we do know people with high Vitamin B intakes are less likely to develop dementia, so every little helps.

Large-scale studies are needed to see if nutrition and exercise can slow the conversion of memory impairment to Alzheimer’s disease. We also need to know if they improve the response to drugs such as donepezil.

For OPTIMA, the next step is a trial of 1,000 people with MCI to see if B vitamins prevent the conversion to dementia over a two-year period. Can AD be beaten? I am optimistic.


Thousands of British MS sufferers to be offered world-first daily pill to battle disease

It's obvious that nothing works terribly well but some relief is better than none

Thousands of people with MS could benefit from the first pill to treat the disabling disease. The NHS rationing body has approved the drug fingolimod which can halve relapses compared with standard interferon injections.

Experts hoped the once-a-day pill will replace injections and hospital infusions for at least 5,000 sufferers a year.

In its initial assessment, the National Institute for Health and Clinical Excellence (Nice) said the drug was not value for money despite admitting it works. But after considering extra evidence on its effectiveness Nice decided to give the go-ahead for use on the NHS.

Dr Eli Silber, a consultant neurologist who leads the MS service for South London based at King’s College Hospital, and was involved in trials, said: 'We’ve waited a long time for an effective oral treatment to offer patients who are continuing to relapse on first line injections. 'Today’s decision increases treatment choice. Because it is a highly effective oral agent it may change the way MS is managed in the UK forever.

'With more active forms of MS, we have a limited window of opportunity to make a difference to patients’ lives - many are young people who are raising families and starting their careers. 'I want to get appropriate patients onto this therapy as quickly as possible.'

MS is the most common disabling neurological condition, affecting almost 100,000 Britons - 50 young people are diagnosed each week.

It involves damage to myelin, a protective sheath surrounding nerve fibres of the central nervous system which means the body’s immune system attacks itself.

Symptoms range from mild, occasional illness involving numbness, muscle weakness and eye problems to rapid and severe deterioration, resulting in serious disability.

Trial results in the New England Journal of Medicine last year showed fingolimod, also known as Gilenya, cut relapse rates and progression of the disease. Patients treated with fingolimod had a 50 per cent cut in disabling relapses compared with commonly used injections of beta interferon.

The chances of progressing to a worse form of the disease were cut by about a third, without significant side effects.

The new drug appears to dampen the immune response that causes nerve damage in multiple sclerosis.

The £19,000 annual cost of the drug compares with the £21,000 annual cost of hospital infusions using Tysabri, and manufacturer Novartis has devised a patient access scheme that cuts the price.

MS specialists say the drug could make overall savings for the NHS, because fewer patients would need hospital treatment costing £3,000 a time after relapse and disability is lessened.

The draft guidance from Nice means it will be funded by the NHS in England and Wales after final guidance is issued next month. The drug, made by Novartis, was rejected for NHS use by the Scottish Medicines Consortium (SMC).

Nick Rijke, Director of Policy & Research at the MS Society, said: 'We are delighted; this decision signifies a major step forward in the treatment of this devastating condition. 'Gilenya has been found to be highly effective in trials and taking a daily tablet will come as welcome relief from frequent, often unpleasant, injections.

'Making this new treatment available will increase patient choice for thousands of people with MS across England and Wales, but we’re deeply disappointed by the SMC’s decision in Scotland - and urge them to reconsider.'

Professor Carole Longson, Director of the Health Technology Evaluation Centre at NICE said: 'Following new information provided during the consultation, the analyses show that for these people (with highly active MS), treatment with fingolimod will be a cost effective option for the NHS, if Novartis provides the drug at a discounted price, as proposed in its patient access scheme.'


No comments: