Restorationof alpha-2-macroglobulin (a broad spectrum protease inhibitor) in blood can cure many diseases.

Mohammad M. Khan, MBBS., PhD. Biomark Bangladesh Foundation, 106, Hosna Centre, Gulshan Avenue, Gulshan, Dhaka 1212, Bangladesh. Author contact:

Reviewed by Naseem Mahmud, MBBS, PhD, DTM, Obstetrics and Gynaecology, United Hospital, Dhaka, Bangladesh.

Recently, we had investigated plasma concentration of A2M, in different patients’ blood (n=31, randomly chosen) who were admitted in a hospital with different kind of diseases in Bangladesh. A2M concentration were 4 fold lower than controls (n=31). In contrast, protease activity level went up, almost 10 fold (1,2,3).

Figure. 1. Proteases were found in different diseases are belonged to following groups.  A2M inhibits all types of proteases.  

Protease inhibitors are used as drugs in many diseases for long time (4) (Table 1). Targeting drugs against different type of protease may be less effective and less successful. But targeting all types of proteases by using a broad spectrum protease inhibitor, A2M may be more beneficial in the treatment of many diseases (Figure 1). A2M inhibits not only protease(s), it is continuously removing redundant chemicals from our body, such as growth factors; cytokines; hormones; soluble beta-amyloid etc. which causes many diseases (1,2,5).

Table 1. Protease inhibitors are used as drugs in many diseases. 

Protease Function Disease Drug/Status
Thrombin Blood coagulation Stroke Argtroban, bivalirudin
    Coronary infarction Ximelagartan, Melagatran
Factor Xa Blood coagulation   Danaparoid (launched), 
      DX-9065a, CI-1031(Phase-II trial)
      DPC-906, JTV-803(Phase-II trial)
      MLN-1021,PMD-3112(Phase-I trial)
Factor VIIa     NAPc2 (Phase-I trial)
HNE elastase Cleaves elastin SIRS Sivelestat (Japan only)
    ARDS Sivelestat (Phase-II trial, USA)
Complement Inhibition Inflammation Nafamostat, FUT-175
HCV HCV repication Hepatitic C BLIN-2061 (Phase-II trial)
PAI (Urokinase)   Cancer WX U K1 (Phase II)
    Aminocaproic Acid (Phase III)
    Ulcer, Psoriasis PAI-2 (Phase-II trial)
Matriptase   Prostate Cancer CVS-3983
Chymase Restenosis NK-3201 (preclinical)
Dipeptydil  Peptidase IV      Diabetes type II LAF-237, P32/98 (Phase-II trial)
Aspartic protease inhibitors in clinic
Protease Function Disease Drug/Status
HIV-1 protease HIV replication HIV/AIDS Indinavir, Nelfinavir,
      Amprinavir, Ritonavir,
      Lopinavir, Saquinavir,
      Atazanavir, Fosamprenavir. 
      Tipranavir (Phase III)
      (monotherapy unsuccessful)
Renin forms Angiotensin 1 Hypertension Aliskiren (Phase II)
BASE forms Ab4 Alzheimers Elan (Preclinical)
      Actelion (Preclinical)
      Locus (Preclinical)
      Astex Technology (Preclinical)
      Sunesi s (Preclinical)
      De Novo (Preclinical)
Cysteine protease inhibitors in clinic
Protease Function Disease Drug/Status
Rhinovirus Viral replication SARS Ruprintrivir(preclinical)
SARS CoV M Viral replication SARS AG7088(preclinical)
Cathepsin K Bone resorption Osteoporesis AEE-58,SB-462795(Phase-II)
Caspase 1 Cytokinine release Arthritis VX-765 (Phase-1)
      Pralnacasan (phase II)
Caspase 3 Apoptosis Cancer, Alzhemier Locus Pharma
    Ischaemia, Sepsis Novartis (preclinical)
Caspase 8 Apoptosis Sepsis, Diabetes IDN-6556 (Phase II)
Cruzain  parasitic replication Trypanosomiasis K-777, INPL-022-E7 (preclinical)
Cathepsin F, L, S     INPL-022-E7, D6 (preclinical) 
Metallo protease inhibitors in clinic
Protease Function Disease Drug/Status
ACE-1 Forms Angiotensin-II Hypertension Trandolapril, Enalapril, Captopril                         
NEP                   Release of ANP Hypertension Candroxatril (discontinued)
TACE Release of TNFa Arthritis, MS BMS-561392 (Phase-II)
MMP-1 Degrades matrix Cancer Marimistat(discontinued), 
      Neovastat (Phase-III)
    Periodontitis Periostat
MMP-2 Cancer Rebimistat(Phase-1)
MMP-8   Osteoarthritis Glocosamine sulphate
MMP-9   Inflammation Rega-3G12, Biopharma
MMP-3,13     Pfizer, Novartis (preclinical)
Threonine protease inhibitors in clinic
Protease Function Disease Drug/Status
Proteosome   Ischaemia Bortezomib, MLN-519 (Phasel)

One day, we might be protected from many diseases by analyzing the level of A2M in the blood, and replenishing diminished levels of A2M in the blood by the method of treatment “A2M-ShopAnn Systems” whenever we fall ill (1,2,3, 6). The onset of a disease only occurs when A2M levels in the body are diminished, thus allowing proteases to harm the body (1, 2). Proteases begin by damaging the body’s defense systems, and, as a result, humans fall ill. Therefore, it can easily be said that, if after a blood test, A2M levels are suboptimal and these lost levels of A2M are replaced in the blood, it is possible to stop any disease at onset. The importance of analysis of the levels of A2M in the blood as well as protease(s) may be a new milestone for the direction of treatment of many diseases and open a new window in medical science (3).

Since A2M is a broad spectrum protease inhibitor, it can inhibit any kind of protease (Figure 1) released in the pathophysiology of diseases. 

This new innovation in the field of medicine may play a vital role in saving lives of all living creatures in the world such as human, plants, fishes as well as whole animal kingdom (6). 


1. Khan MM, Muqueet MA, Hossain I, Khan ME, Shibli MH, Mustavi I Hossain M, Hossain ME 2016 Measurement of protease activity and concentration of a broad spectrum protease inhibitor; alpha 2 macroglobulin (A2M) in plasma of severely chronic ill patients in Bangladesh. J Clin & Exp Pathol. 6:4:288

2. Khan M.M., Muqueet M.A, Hossain I., Khan M.E., Mustavi I., Shibli M.H., Hossain M., Hossain M.E. A cross-sectional study to estimate the prevalence of protease activity in the plasma of chronically ill patients in Bangladesh and identify its predictive relationship with protease inhibitor, alpha 2-macroglobulin (A2M). 2016.  (Online Journal:

3. Khan M. A2M-Miracle Protein, the lifesaver.

4. Leung D, Abbenante G, Fairlie DP. Protease inhibitors: current status and future prospects. J Med Chem. 2000 Feb 10; 43(3): 305-341.

5. Armstrong PB. Proteases and protease inhibitors: a balance of activities in host-pathogen interaction. Immunobiology. 2006; 211(4):263-81.

6.  Khan MM. (Short Research Communication) 2016. A new concept on prevention and cure of diseases by a broad spectrum protease inhibitor (A2M). (Open Access journal) International Journal of Current Innovation Research, Vol. 2, Issue 11, pp 523-528, November 2016

 Submitted to Rare Diseases India on March 19, 2017.

Book on this subject:
A2M-Miracle Protein, the lifesaver By Mohammad Khan MBBS PhD
Publication Date: January 15, 2017
Book Size: 6" x 9"
Pages: 51
Binding: Spiral Bound
ISBN: 9781946634290