Chocolate Biscuits – Does genetics hold the key to MND/ALS?

Arhh an interesting and be-musing title. Read on viewers to gain insight into the inner workings of my mind. You will have to wait a bit for the biscuits, however.

I finished my last post asking the question when does the disease start? The general consensus is that it is a combination of genetics, time, environment and chance.

DNA – By brian0918™ (Own work) [Public domain], via Wikimedia Commons

Wow, as I was writing this post I did think “What do you want to say Lee?”

Well in one sentence, I wanted to give you some information to explain why I think genetics will lead us to a therapy. It is also important to state, that although I am talking about MND the principles apply to many complex diseases.

Current research shows that about 90/95% of all cases are sporadic with no genetic link as yet shown? So how exactly are genetics going to help us?

So let me take you on a short trip in time (spooky)…….., it is some 200 years ago, even before HG Wells had written the Time Machine. It was the era of Charles Darwin, the father of evolution. However, there was also this man…..

Jean Baptiste Lamarck

Lamarck proposed that evolution was built on what he called, acquired characteristics. His proposition was that things that we experienced in life may/can be passed on in some way to our offspring. He was largely ignored and Darwin’s theories prevailed.

“Lee, where are you going with this interesting but rather annoying history lesson?”

“Calm down, Calm down readers, there is a point”.

Foot to the floor, fast forward to 1985. I had a terrible moustache

and I had just graduated from Imperial College after studying Biology. Computers barely existed, mobile phones didn’t exist and genetics was really getting interesting. I loved science, and genetics, but like a lot of people ended up in computers. Geneticists and Biochemists were generally poor, and I wanted a car (An XR3i to be precise).

Memories….here is that wonderful car after getting married.

Back then people used to tie anything to cars when you were married, dustbin lids, road traffic signs etc! Arhh don’t you just long for the days before health and safety! What was wrong with a few sparks down the motorway anyway? Airbags? What were they?

Brake!!!!!!!!!!!!!! Lets go back again, this time to the 1950-s when Down’s Syndrome was traced to a genetic fault. Down’s is an interesting genetic condition as it touches on one of key aspects of disease and genetics which tends to remain hidden, and that is the element of time. We don’t know why the mistake happens, but it happens increasingly with maternal age (dramatically increases over age 35).

Over the next 50 years there was nothing less than genetic revolution, and our understanding was increasing by the day. In 1985 DNA profiling appeared, and is now an everyday occurrence in criminal and paternity cases.

Now for a staggering fact. I remember when the first whole Human genome was sequenced, in 2001. Not only did it cost about £200M for one human genome, but it took about 15 years! Today in 2015, it is about £1600 and takes 7 days! It is this cost that is changing everything.

So history lesson over and hopefully all will now slip into place.

But before that, some biscuits..

I like analogies, and my little crumble of the choc digestive above is not the result of a ferret attack! It’s another bit of information. I use this to show how much of the human genome actually codes for proteins. Its only about 1%. Why is this important? Well the majority of genetic work has been done on this bit alone. To do the whole thing requires whole genome analysis, and remember the cost of that!

So let me get to the point…

In 1993 we had identified one gene associated with MND, now it is four major genes with about a hundred implicated! However, it is complex, and having any one of the known gene mutations doesn’t actually mean you will definitely develop MND, and we still have the 90/95% of sporadic cases.

Coming right up to date.

So now with cost of whole genome analysis having dropped dramatically, we are now able to do what ProjectMinE has just started.

ProjectMinE is fully sequencing over 20000 MND sufferers and control subjects. This has never been carried out before. Size is important, and the 20000 genomes will enable true statistical differences to be detected.

This project is going to find some secrets, and it is for this reason that it is my pet project for donations. I believe that our best chance of finding a therapy is to understand the full disease model, and my opinion is that we find this in the human genome.

Has this technique worked before? The answer is yes. And its a big yes. HIV/AIDS no less. About 1% of all people infected by HIV never get sick. Through analysis of this group a genetic variation was found! A drug was developed to enhance the effect of this mutation that could be used for all sufferers, and it is effective.

With MND, the rate of decline of sufferers is varied. There are some who survive over 10 years and even decades. Why? These patients make a great study group and may provide a similar solution.

Lee, what about Lamarck? You went to all that bother to introduce him!

Good point, eagle eyed readers and it is probably the crucial point! Well, elements of Lamarckism are alive again today, in the study of epi-genetics. Put simply, we now have evidence that our DNA changes during our life (another time factor). These changes even 10 years ago were not considered possible. These changes can lie in the area of the genome which does not code for proteins (the big bit of my biscuit). It is believed that the large part of the biscuit controls or regulates the 1%.

I hope you enjoyed my ramblings. It was a big one this week!

And the irony of my choice to venture into computers in 1984 – is that now modern genetics is simply that. Geneticists are mathematicians and computer analysts. 

Back to the future so to speak!

Anyway until my next post, which won’t be about genetics, but genetics will be back. And……….

“I’ll be back!”