Designer DNA drugs to soon conquer ailments like Alzheimer’s, Parkinson’s

Designer DNA drugs that are promising to conquer modern world’s ailments of the aged like Alzheimer’s, Parkinson’s and others related to the human Brain are round the corner.

Atleast five drugs are in the advanced stage of clinical trials. They are targeted at inherited ALS (Amytropic Lateral Sclerosis), Spinal Muscular Atrophy (SMA), Huntington’s disease and Alzheimer’s.

While Ionis Pharmaceuticals, a startup in the United States (US) is involved in four of these promising drugs, Roche, the Pharma major is carrying out phase-3 trials for Huntington’s said Don W Cleveland, the man behind the promising breakthrough.

In a career spanning over four decades, Cleveland has made leading contributions in cancer genetics and neurosciences. He is currently the Professor and Chair of the Department of Cellular and Molecular Medicine at the University of California at San Diego.

In December 2018 he received the $3million Breakthrough Prize in Life Sciences for his development of a new class of “designer DNA (Deoxyribonucleac acid) drugs” for silencing disease-causing genes responsible for the major diseases of the nervous system. He also received the Genome Valley lifetime achievement award at the BioAsia conference held here.

In a free wheeling chat with BusinessLine, the renowned neurobiologist narrated the doubts, hopes and promises of these class of drugs in the future.

Early Days

In 1977, I discovered Tau, a protein which accumulates in Alzheimer’s disease. It is this protein whose misfolding causes chronic traumatic brain injury. “The discovery was more serendipity”, he recalled.

Pharma companies used to call this protein ‘undruggable’ for long. Around 2006, Cleveland and researchers developed gene silencing therapy for neuro-degenerative diseases by silencing or switching off the bad genes within the affected neurons.

Initially, the developments were viewed with scepticism and was also told that they will not work said Cleveland. “We doggedly pursued. I saw my own father die of Parkinson’s and followed every phase of the degenerative disease”, he recalled.

Big and promising success

One of the biggest success so far in this novel treatment approach has been achieved in Spinal Muscular Atrophy (SMA). In the US one in a 1000 kids are affected by this problem. A drug, Spinraza from Ionis Pharmaceuticals has been approved by the United States Food and Drug Administration (USFDA) in December 2018. Atleast 400 kids treated are now able to walk, Cleveland said.

Lack of a key protein causes the motor neurons in patients’ spinal cords to whither and die, but, using a specially-designed DNA drug, researchers have been able to fix a critical error in messenger RNA, allowing a very similar substitute protein to be produced.

“Now they have kids who are walking, kids who never could move, for those families, it’s a miracle,” Cleveland explained.

The 68 year old Cleveland told the American Neurological Congress recently, “It’s a big change from where things were a decade ago”.

“I wouldn’t have even been invited to speak to a meeting like that, because no one thought it could work. We’ve really gone from total skepticism and outright criticism to a feeling that these drugs are just obvious and inevitable,” Cleveland said.

So 42 years after identifying the protein Tau, a dozen years after demonstrating how genes can be silenced, we are on the brink of seeing the unfolding of an era of a new class of drugs ( from undruggable to druggable) that attack and provide relief or cure to patients suffering from neurodegenerative diseases.

India is familiar, came on honeymoon

For this accidental neurobiologist, India is a familiar country having visited it for the first time in 1981 on a honeymoon trip. “ We travelled to Chennai and experienced winter rains, then to Jaipur, Khajuraho and Delhi”, the 65 year old Cleveland recalled.

My father was a Physicist. He wanted me to follow him, so I took up Physics. But I could not finish, so switched to biochemistry, said the Mexico born scientist. This is his sixth visit to India.

India is a fast emerging global technology centre, its population diversity offers immense scope for research in modern genetics. There is good chance for collaborative research with Indian research institutes too, he felt.

What did he do with his $3million breakthrough prize of 2018 for discovery related to ALS?

“I donated most of it to causes related to our work, especially to Doctors without Boundaries. “I never wanted to make lot of money, but somehow keep getting. Get paid a lot for what I like to do”, he says in a light hearted way.

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