New gene finding suggests recycling is key to all forms of MND

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Researchers from Northwestern University Feinburg School of Medicine in America, have identified that faulty ubiquilin 2 plays an integral role to MND.

Led by eminent researcher Prof Teepu Siddique this research group describes unique mistakes in a gene called UBQLN2, which codes for a protein called ubiquilin 2, in five families with the inherited form of ALS. This research group also found that this protein is found in both the inherited and sporadic form of MND, which suggest that this finding could be key to finding a new treatment for the disease. Their findings were published in the prestigious Journal Nature.

What did the researchers do?

The researchers started by identifying a novel genetic mistake in a gene called UBQLN2 for a family affected by the inherited form of ALS. ALS is the most common form of MND. They went on to duplicate this finding by identifying four more genetic mistakes in the same gene in four other families with inherited ALS. This verified that this finding is not simply a ‘one off’.

By examining post-mortem spinal cord samples from people with ALS within these families, faulty ubiquilin 2 was identified as being involved in forming ‘tangled lumps of proteins’ within their motor neurones. When a researcher looks down a microscope at a motor neurone with the disease this ‘tangled lump’ is a classic sign of MND.

The next question that this research group addressed was whether ubiquilin 2 could also be found in other forms of MND. Remarkably, by studying post-mortem samples of people with the randomly occurring ‘sporadic’ form, inherited form (caused by mistakes in SOD1, TDP-43, FUS or an ‘unknown’ gene) and fronto-temporal dementia – related MND, they identified ubiquilin 2 within the ‘tangled lump’ in all of the samples.

This means that ubiquilin 2 could be the ‘smoking gun’ of MND.

Never before has one single protein or gene been related to all forms of ALS. Until now.

Mistakes in this gene are very rare and as yet, we don’t know how many cases of inherited MND are caused by it. This discovery does not open up the possibility of a new genetic test to identify people who might be at risk from the disease, but it does provide a new and exciting insight into the causes of all forms of MND.

How does ubiquilin 2 cause MND?

Imagine a world where all recycling collectors are on strike. Every Wednesday at 7am you place a box of recycling on your driveway ready to be collected, but it’s still there in the evening. The next week you put out more recycling, and that isn’t collected either. After weeks of putting your recycling outside, you notice that the pile is mounting and still isn’t being collected. This doesn’t bother you too much as you can still step over it, albeit in a slightly slower manner. A few months pass and you can no longer get out of your driveway as it’s covered by recycling. Now you can’t get rid of your rubbish, you can’t get to work and you can’t even leave your house all because of the pile up of recycling. The same thing is happening to everybody all over your town. This is what happens in MND.

One of the pathological hallmarks of MND is a build-up of ‘recycling bins’ of proteins in motor neurones. Normally, these recycling bins are emptied on a regular basis by a process regulated by a family of proteins called ubiquitins – of which ubiquilin 2 is a member. This build up of recycling causes pandemonium in cells, as vital movement of nutrients around the cell cannot easily pass to where they need to get to, causing an additional burden to the motor neurones. Eventually, the motor neurones start to degenerate because of this.

What now?

These results will now need to be verified in more people with MND. However, this study could revolutionise the MND research world and provides evidence that the recycling pathway plays a crucial role in MND. Researchers now need to find out how the recycling pathway is involved with MND which could provide insights into how new treatments could be developed to target the disease.

We’ll be keeping a close eye on ubiquilin 2 in the future!

Read our press release on this news story.

Read the Scotsman article on this story.

Reference: Nature (2011) DOI:doi:10.1038/nature10353

UPDATE: Prof John Mayer from University of Nottingham takes you even further behind the scenes of this news story.

25 thoughts on “New gene finding suggests recycling is key to all forms of MND

  1. This is a major breakthrough in research – quite mindblowing and hopefully will start a rush to identify a treatment and ultimately a cure. Here’s hoping it comes through.

  2. This is great news for everyone.. especially my family.. having a grandfather, Father, and a Aunt die from this is more then any family should take…. Keep up the remarkable progress researchers…

  3. Nothing is Great!!
    It’s just a Hype for a good but not extraordinary work.
    The Same we See with othrr diseases too.

  4. My fiancee, aged 29, was just diagnosed with ALS on 8/25/11. This is the most encouraging news I have heard thus far. Praying for a cure so my fiancee can see his baby grow old.

  5. harry pavlou my brother was diagnosed in aug 2007 please please god let this be a cure and quickly

    1. You’ll find an update on this new story in a new blog post:

      The implication, is that a possible common MND causing mechanism has been identified. We don’t yet fully understand how ubiquilin 2 can cause MND, so this will be the next steps for researchers. Once this is understood, then drug discovery programmes can try to target the process that is going wrong to develop new treatments.

      I hope this answers your question, if you have any further questions, please email us at

    1. Hi Paul,

      You may have seen that we published a similar news story yesterday regarding another recycling gene being linked to MND. This suggests that the recycling system should be placed near the very top of the list of ‘important things that go wrong in MND’. Combined with the fact that this process can be disrupted in other diseases, such as Parkinson’s, this may provide more assurances to pharmaceutical companies that investigating this process and devising treatments that can help this system may be beneficial for diseases such as MND – including PLS. Although this story doesn’t yet result in a treatment, or have any direct benefit now, it definitely opens up another door for researchers to find treatments that really have a hope of fighting all forms of MND.

      Hope this answers your question.

      1. Thank you for the prompt reply and the answer within. Lets hope the future brings a positive outcome for everyone who is effected directly or indirectly.

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