You may have a look to this Research topic in Frontiers

Successful therapies for Alzheimer’s disease: why so many in animal models and none in humans?

Article Successful therapies for Alzheimer’s disease: why so many in...

Also, there are difficulties in assessing neuroprotection; I mean that it is not easy to get a drug approved for neuroprotection. Wich parameters you may meassure and are approvable by FDA for neuroprotection?

Last but not least there is lack of money for clinical trials to test promising drugs but whose patent has been already finished and are generic. We tried to implment a clinical trial with patients to test an "old" drug that is safe and with excellent results in animal models and wer unable to find money.

Thanks for the answer and you understand the question well!!

By dementia I know this problem but I as an therapist in an Nursing Home have an complete different patient in my hands that I must treat at the best of my knowlegde and skill and than it is poor to read never an article about this group of patients. There must be an way to coporated on the floor because that will show the scientist what the end is and the therapist has someone that think with him.

Which clinician could afford to contemplate Dominik Meier's unquestionably stellar MRI sequences of a patient with multiple sclerosis? 

Or ponder their therapeutic implications?

 https://medium.com/@franzschelling/what-deals-the-brain-such-blows-synchronous-at-least-double-hits-in-an-exemplary-case-of-292877844500 ...  http://bit.ly/2hu3g9N

Think about physical causes of an immune disease?

I agree with previous answers, we work with experimental models that usually only cover a facet of the real disease, plus in these models typically the disease is accelerated so pathology it takes years to occur in humans it happens in weeks or even days in the model.

Then we find compounds that work pretty fine in the model scenario, but when tried over the real disease the impact is a lot lower, often by compensation mechanisms, plus by side effects or toxicity.

In neuroscience processes are very long, many years, in other fields, eg. infectious diseases, once the pathogen is killed in few days work is done, so it is a lot more easy to move from experimental model to real disease.

To make a simple analogy, when some machine breaks by wearing out is relatively straightforward to do a temporal fix, but to make that fix permanent is basically impossible, because the places where the fix is anchored are then going to break down.

In conclusion, we will benefit of better models, but very people is really interested on developing these because the investment is elevated and the reward is at very long term. Science nowadays favour short term investments.

Sorry, Dr. Mustafa Ali Khan, which point of my comment on Dominik Meier's MS video did you want to address?

The problem seems to be that

"Unmistakable MS lesions reflect retrograde venous impacts in a tell-tale MRI series"

Please share my non-factional look at Dominik Meier's unquestionably stellar MRI sequences of a patient with multiple sclerosis. 

Doesn't https://medium.com/@franzschelling/what-deals-the-brain-such-blows-synchronous-at-least-double-hits-in-an-exemplary-case-of-292877844500

or  http://bit.ly/2hu3g9N indicate: 

Such cases of multiple sclerosis are biomechanically primed hemodynamic and obviously venous conditions. 

Which need to be established as such, to be addressed with the adequate technical equipment and topical expertise. 

It was great if you granted me some feedback on this initiative. 

Sincerely

F. Schelling, M.D.

There is vast amount of research going on and conducted in terms of simpler models (cell culture, primary cultures and small animal models) to address the neurological diseases or CNS trauma models; but in the end you will get the answer that these models may not exactly replicate the human condition and that's why they failed. In, most of the animal models, drug metabolism, toxicity and other factors are not completely established; lab to lab variations in model establishment; per-treatment strategies (which may not have any relevance); invasive drug delivery methods (eg., icv) may show benefit in pre-clinical models but their practical utility when it comes to humans is minimal. When human brain is so complex and has number of variables, how can a simpler cell culture studies provide any answer, but lot of efforts are concentrated on these simpler models without much use. Of course larger animal research has its own limitations and ethical issues. AD: For Alzheimer's sporadic diseases dominates the familial one; having models for sporadic disease is a challenge; let alone for AD for many CNS disorders. Numerous drugs that showed excellent efficacy in pre-clinical models failed in human trials. However, there are drugs that failed in Parkinson's Disease treatment showed benefit in MS. One school of thought is pursuing for new drugs should continue; but at the same time the drugs that failed in clinical trials need to be given another chance in modifying the treatment strategies, route of delivery, formulation, or for another disease treatment. Stroke: One of the drugs for stroke treatment citicoline branded as a failed drug in stroke treatment (administered orally; 24 hrs after stroke; although it is well known for stroke first 3-6 hours are critical). This drug's metabolism is not properly considered in humans, nor the timing of administration. Liposome encapsulated drug showed benefit in pre-clinical models; and this option was not ever seriously considered before branding this agent as a failed drug. It is not the drug, but the way it administered or formulation all these matters before giving up. Since most of these drugs that failed at the clinical levels have gone through extensive ADMET studies and researchers/clinicians should consider whether these drugs can be utilized in another form, route or for another disease before abandoning them since lot of effort and money spent on these studies.

Blood-brain barrier (BBB) is one of the challenges that impedes drugs effectively to reach the brain. Drugs to cross this barrier and enter the CNS/Brain is a challenge. You may have a effective drug, but effective formulation, or route of delivery comes into picture due to this complexity. Brain's lipophilic (lipid or fat soluble) nature and agents hydrophilic (water-soluble) nature makes the drug entering the brain in sufficient concentration makes the problem complex. There are diseases/injuries that makes BBB breach/breakdown; this has its own benefits and disadvantages. BBB breach allows drug to reach brain at the same time toxic materials also.

Not explained neurological dysfunctions are explained (ever anew) by the disease causes which are the focus of the mainstream research of their time. If the explanatory tenets of mainstream research do not comply with specific physical phenomena which attend the dysfunctions ... the worse for the physical phenomena!

To stick to the question at hand, regardless of the suggested model consisting of clinicians, therapists, researchers and other parties and how they communicate (which is a fair and correct point). It is inherent to any (para-)medical profession and to any researcher to be sceptical when information is given that changes the current paradigma of a subject. Before research reaches the therapist for the therapist to implement, several "I don't believe this, I have to check for myself" layers have to be conquered. This takes time. This is readily exposed in the more elderly health professional, who hold on to their therapies and explanatory models that were the state-of-the-art 40 years ago. The world develops, in each and every aspect, quicker than a sceptic can cope with. That's why educational programs are more inclined to teach you how to learn rather than to teach you the facts nowadays, and self-reflection is becoming more and more integrated in all layers of health care.

I totally agree !! Still I am an old physical therapist and i feel almost never the "drive "from the scientist to participate in the problems of my patients.

This is the group living in an nursing home with ënd Stages"of neurological diseases but still my quenstions are not taken in an investigation.

May I gice an example : the theory of the diagonals that are obvious in walking are also active in supine situation. Lifting one leg ask for an stabilisation of the body with the other and that evoke by neurological siseases an extension synergy and give an striker foot.

Thanks for searching your ideas

greetings jan

Rik, making the resolve of "I have to check for myself" has at times quite untoward consequences!

I do not deny the value of scepticism, Mr. Schelling.

Just a theory, the missing "drive" to help patients could be derived back to a more philosophical sense of meaning. Many scientists are in the work field not only to help with progression, but also to find truth to a question that was left unanswered. Such a passionate will to find the truth is indeed very important in science, but it may also cause a gap between researcher and patient. More simply put, finding "the answer" may sometimes be the end of the line for many researchers, rather than bringing the answer to the rest of the world.

Mr. van de Rakt, it may perhaps prove useful to file case reports of findings you wish to be researched. Case reports are a dire necessity in the process of science and should not be underestimated!

This is a thoughtful clinical question. The beauty of this platform is that you receive sound and diverse scientific/clinical responses that are truly enriching.

The simple fact is that laboratory approaches are purely controlled and consciously directed towards finding solutions to set problems. Unfortunately, replicating such situations in real life clinical setting becomes difficult or only possible to certain extent. It is imperative on scientists and clinicians to collaborate from the outset of research formulation to pull their varied experiences together to ease translation of research findings.