mTORopathy: an emerging buzzword for neurology

I was recently perplexed with my first case of tuberous sclerosis complex (TSC). I had no idea what treatment, monitoring and surveillance I needed to institute. I quickly checked things up in neurochecklists; I found excellent checklists on the pathology and clinical features, but was disappointed that there were no treatment or monitoring checklists. I quickly hunted down TSC diagnostic criteria and TSC surveillance recommendations and updated neurochecklists. Phew!

By Herbert L. Fred, MD and Hendrik A. van Dijk - http://cnx.org/content/m14895/latest/, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=11892420
By Herbert L. Fred, MD and Hendrik A. van Dijk – http://cnx.org/content/m14895/latest/, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=11892420

In the process I discovered that TSC features may improve on treatment with a class of drugs called mTOR inhibitors. Highfalutin stuff I said to myself, and thought nothing more of it. I had to reassess my opinion very shortly afterwards when I came across the Association of British Neurologists (ABN) SoundCloud page with ABN President Phil Smith interviewing Ingrid Scheffer on epilepsy genetics.

We have all experienced that disquieting feeling of just learning something new, and then seeing it crop up all over the place. This is what I felt when Ingrid Scheffer casually stated that Tuberous Sclerosis is an mTORopathy. mTOR is big enough to be an ‘opathy‘, and I was completely ignorant of it! And how come I haven’t heard of Ingrid Scheffer before now-serves me right for missing the last ABN conference in Brighton.

I decided to dig a bit deeper and here are 9 things about mTOR I discovered:

1

mTOR stands for mammalian (or mechanistic) target of rapamycin

2

mTOR is a kinase

3

The mTOR pathway is important in regulating cell growth and cell death

4

mTOR has an important role in many disorders (mTORopathies). These include tuberous sclerosis, epilepsy, autism, traumatic brain injury, brain tumours, and dementia

5

Mutations in TSC1 or TSC2 genes cause hyperactivation of the mTOR pathway

6

mTOR inhibitors are under investigation for the treatment of these diverse diseases

7

Sirolimus is the major mTOR inhibitor

By Fvasconcellos - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=1549073
By FvasconcellosOwn work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=1549073

8

The DEPDC5 gene regulates mTOR inhibition.

9

The DEPDC5 gene is mutated in many neurological disorders such as familial focal epilepsies, focal cortical dysplasia, and epileptic spasms. These constitute DEPDC5 motoropathies.

+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

Enough information to tickle the little grey cells but if you want to dig deeper than you may follow these links:

4 thoughts on “mTORopathy: an emerging buzzword for neurology

  1. Dr Ibrahim,
    I really appreciate your updates-they are very clear and succint, and I must say, they really help in quick understanding of complicated topics. Thank you very much.

    Like

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s