Update on promising drug NU-9

Positive results in mouse studies

Whilst the focus is on MND (motor neuron disease) with this drug candidate currently, Dr Ozdinler has flagged this compound as having potential for treating HSP.

NU-9 lengthens axons of diseased neurons better than current FDA-approved drugs for MND

New drug’s effect is enhanced when given in combination with existing MND drugs

If the animal studies go well and the FDA approves, NU-9 could be in clinical trials in early 2023 

CHICAGO — New research on the experimental drug, NU-9 to treat MND (motor neuron disease) otherwise known as ALS (amyotrophic lateral sclerosis), shows it is more effective than existing FDA-approved drugs for the disease. 

More importantly, NU-9 has an enhanced effect when given in combination with those drugs, riluzole and edaravone.

The research, published recently in Scientific Reports, showed NU-9 lengthened the axons of diseased upper motor neurons in mice with MND model.

The axon is the segment of the upper motor neuron that connects the brain to the spinal cord and makes the corticospinal tract, which degenerates in people with MND and HSP.

“For a drug to be effective, it is important for that drug to improve axon outgrowth and axon health,” said co-lead study author Ozdinler. “This is very important for connecting the brain and the spinal cord and for revitalizing the motor neuron circuitry that degenerates in patients.”

NU-9 moving toward clinical trials

AKAVA Therapeutics is carrying out animal safety studies needed for the drug (now called AKV9 in the company) to receive FDA approval to become an Investigational New Drug. Those studies include determining dose level and toxic effects. 

“If everything goes well, we hope to start with healthy volunteers in a Phase 1 clinical trial early in 2023,” said co-lead study author Silverman.

“It is a long process – possibly 10 to 12 years – to discover and bring a new drug to the market,” Silverman said. “But this drug has us very excited and hopeful about its possibilities to improve the lives of ALS patients, who have been without hope for so long.“

Read more…

SOURCE:  Eureka Alert NEWS RELEASE 17-MAY-2022

New ALS ‘drug’ is more effective than existing ones

Northwestern University


  1. This says it takes 10-12 years to bring a new drug to market. If everything went perfectly with the clinical trials for NU-9, is that the earliest patients could receive this medication? Time and hope are so important to these patients. Why do they test the drug on healthy people first if the drug’s effects are meant for people with MND?

    1. Editor’s note: The timeline to market for a drug in this stage of development may be as little as five years. The timeline can vary depending on the priority/funding it is given by the pharmaceutical developer; the priority it is given by regulators – this can depend on disease prevalence, disease impact, drug or disease categorisation e.g. repurposed drugs and/or rare disease classification may get special treatment such as fast tracking; and of course, technical considerations in the research process, which are usually numerous and significantly challenging e.g. characterisation and measurement of disease status and changes in disease status; discovery and development of suitable assays or tests for clinical trials, and so on.

      The first requirement (phase 1) in any clinical trial is to establish the safety and tolerability of the candidate treatment, administered at a particular dose/frequency, by a specific method e.g. oral medication, intramuscular injection, nasal spray etc. This is best done in healthy people. Preliminary effectiveness is not tested until phase 2. Clinical trials can be long and trying for people with a medical condition – sticking to the program of medication, continual monitoring and testing; so delaying their involvement until necessary is easier on them and reduces dropout rates amongst participants.

      1. Do you know if NU-9 will be indicated for ALS patients only? I take Amprya off-label but it is a generic that isn’t covered by my insurance so it is expensive. I also recently asked my neurologist about using ALS medications that slow upper motor neuron degeneration instead of just treat symptoms of this disease. To acquire these medications, he would have to prescribe them off-label since they are not indicated for HSP but insurance doesn’t cover these meds. He told me that one I wanted to try, Relyvrio, was going to cost over $100,000 annually. So will NU-9 be the same?- be indicated for ALS, not HSP and be financially unattainable for patients with our disease? Are there programs that help patients with our disease get off-label medications at more manageable costs?

        1. Editor’s note: The current research is aimed at ALS, so if NU-9 proceeds to clinical trial, it will be for ALS only. Until a treatment is tested and approved for a particular condition, the current situation of off-label prescribing will likely remain with the associated high costs. The main focus of government policies to deal with this situation for rare diseases is to facilitate testing treatments/doing clinical trials in these diseases. Once safety and effectiveness of a particular treatment for a disease is established – and that is an essential process – hopefully the treatment would be covered by insurance (in the US) and/or by government programs such as the PBS in Australia or the NHS in the UK. There are no programs anywhere to help get off-label medications at manageable costs, the reason being that safety and effectiveness are not established.

          1. Ok, sorry if this sounds blunt or stupid, but im not a scientist & my HSP has progressed fast enough that I’m really struggling to do my job so I’m an emotional wreck. Anyway, this is disheartening. So HSP patients will have to wait until this drug completes all stages of clinical trials for ALS patients (you said this could take 5 years in an earlier message) and then we won’t be able to get this medicine unless we are rich because insurance won’t cover it because it’s not been tested for HSP people so we’ll have to get it off-label. Can you break down the cost of clinical testing at least for the process in the efficacy stage? If NU 9 finishes and passes the first stage of testing for safety, couldn’t we get 50 HSP patients together & all trial it for efficiency with regular evaluations & not just help ALS patients? Or why don’t we do this for other meds that slow neuro degenerative processes for MS or ALS patients? If the med is available & FDA approved, what costs so much that we can’t try to help others with these meds?

          2. Editor’s note: A pre-clinical investigation program to test NU-9 in HSP could start any time – If funding was available; if approval to use NU-9 for this purpose was gained; and if a research team to do the work was willing. Dr Ozdinler, part of the NU-9 ALS research team, also does research in HSP and may already have initiated studies in HSP. Pre-clinical investigations in HSP would be needed before a clinical trial because regulatory approval for a clinical trial depends on evidence in cell and/or animal models that it is effective. The disease-causing mechanism in ALS is different to the HSPs and there are at least five different disease-causing mechanisms within the 90 or so forms of HSP currently described. The studies would need to focus on one form of HSP. The NU-9 molecule, now known as AKV9, is owned by Dr Silverman, so its availability for research studies depends on him. Scientists tend to be circumspect about their research plans to protect their intellectual property and discoveries, so there may be plans already for investigation of this compound in HSP that are not publicly known. The costs of pre-clinical investigations and securing FDA approval for a clinical trial are themselves quite substantial (could be over $1 million). If safety and tolerability are established in an ALS clinical trial, and if the effective dose range for HSP is found to be the same as for ALS, then phase 1 of a clinical trial may not be required for HSP. However, the rigourous requirements of recruitment, methodology, monitoring and measurement for a phase 2a study of preliminary effectiveness make it impossible to do a “let’s just try it and see” approach to any drug testing in humans for which regulatory and market approval is sought. Any investigational drug for any form of HSP would need to be formally evaluated, firstly in pre-clinical investigations, and then in clinical trials. Neurodegenerative processes is a generic term covering different disease-causing processes and mechanisms. The pre-clinical investigations are necessary to identify and specify the exact nature of these processes and mechanisms in any given form of disease, which then points the way for drug screening. It is also common that assays to measure impairment or drug effect need to be created or developed as a significant part of rare disease research is ‘discovery learning’, so assessment and measurement become very significant factors. The costs of setting up the documentation for a clinical trial as well as measurement, recording, monitoring, data analysis and reporting are all substantial, as independent third parties must be involved in and oversee these functions.

  2. Does lengthening the axons just result in the maintenance of current mobility or does it mean patients could regain lost neuromuscular function?

    1. Editor’s note: When this question has been put to clinician/researcher neurologists, some have said that if regeneration of impaired axons can be achieved as a result of treatment, then, theoretically at least, impaired functions could be regained to some extent. The only way to know is by testing in clinical trials. The opinion has also been expressed that physical rehabilitation programs of movement and exercise could well be necessary to maximise the potential for restoration of impaired function, especially with longer term impairment of gait and mobility in people with HSP.

    1. Editor’s note: Available information on progress will be reported here every quarter, but three months is not a long time in research terms, so don’t expect an update on this drug every quarter.

  3. We really need to test HSP with NU-9! This would be HUGE!! So many people suffering from this disease. We need hope. I am tired of neurological diseases being ignored.

  4. I am a young 70 yr old newly diagnosed with ALS… started with drop foot. Will these trials with Nu-9 be offered in Canada? If not will Canadians be allowed to participate in the trial by travelling to the States? Very excited about your product, gives ALS patients hope:)

    1. Editor’s note: The developers of NU-9, who are based in Chicago, will widely publicise where and when trials may become available for participants. At that time, inclusion/exclusion criteria for potential participants should be available. We will continue to report on developments with this candidate treatment.

    1. Editor’s note: It would be way too early for that. The company that is developing the drug foreshadowed the possibility of a phase 1 safety and tolerability trial in healthy people in the first part of this year, but there is no sign that has happened as yet. ALS is their primary target but it is hoped that its potential for treating HSP can be evaluated.

  5. The SP-FOUNDATION is supporting your efforts for NU-9. We are giving you money for HSP research so I hope to God that HSP patients will be able to try this soon! Or my fundraising is pretty much garbage.

  6. I have a good friend in Australia with recently diagnosed upper and lower limb classic ALS with possible bulbar involvement. He is very interested in any clinical trials and said he is more than willing to be “a lab rat” given his current prognosis. Any advice on how he might pursue this course of action would be greatly appreciated.

    1. Editor’s note: Suggest you/your friend seek guidance from ALS support groups in Australia and/or the US. The drug candidate NU-9 is being developed at Northwestern University in Chicago. If/when clinical trials with this potential ALS drug materialise, communications and publicity on the trials and how to participate will come from these ALS groups.

    1. Editor’s note: This research is being done in Chicago with no relationship to this Foundation. We are merely reporting on progress. If and when a clinical trial is initiated, it is highly likely to be focused just on ALS (motor neurone disease). There may be subsequent clinical trials on different conditions such as PLS or HSP depending on the results and outcomes of the initial trial.

  7. Is NU-9 developed for all ALS patients? I read that they are researching on SOD-1 mouse models. Thanks.

    1. Editor’s note: You may find information on that question on an ALS support group website. Such questions may only be clarified once clinical trials are imminent.

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